Unrelieved pain in acutely ill patient

Reasons for the undertreatment of pain

1. Inadequate knowledge and skills to assess and treat pain.
2. Unwillingness to believe patients' report of pain.
3. Lack of time, expertise, and perceived importance of making regular pain assessments
4. Inaccurate and inadequate information about addiction, tolerance, respiratory depression, and other side effects of opioids.

Patient-related reasons for undertreatment of pain

• Fear of addiction, tolerance, and side effects.
• Belief that pain is the inevitable result of worsening disease, and the expectation that the drugs will not relieve pain.
• The belief that pain is inevitable and the desire to be a "good" patient who does not complain.
• Particularly common among older adults.

Harmful effects of unrelieved acute pain

• Endocrine/Metabolic pain response
• Increased adrenocorticotropic hormone (ACTH)
• Increased Cortisol
• Increased Antidiuretic hormone (ADH)
• Increased Epinephrine and norepinephrine
• Increased Renin, Increased aldosterone
• Decreased insulin
• Gluconeogenesis
• Glycogenolysis
• Muscle protein catabolism
• Possible clinical consequences
• Weight loss (from increased catabolism)
• Increased respiratory rate
• Increased Heart rate
• Shock
• Glucose intolerance
• Hyperglycemia
• Fluid overload
• Hypertension
• Urinary retension
• Urinary retension, decreased urine output
• Cardiovascular pain response
• Increased heart rate
• Increased cardiac output
• Increased peripheral vascular resistance
• Increased myocardial oxygen consumption
• Increased coagulation
• Possible clinical consequences
• Hypertension
• Unstable angina
• Myocardial infarction
• Deep vein thrombosis
• Respiratory pain response
• Decreased tidal volume
• Hypoxemia
• Decreased cough and sputum retention
• Possible clinical consequences
• Atelectasis
• Pneumonia
• Renal/Urologic pain response
• Decreased urinary output
• Urinary retention
• Possible clinical consequences
• Fluid imbalance
• Electrolyte disturbance
• Gastrointestinal pain response
• Decreased gastric and intestinal motility
• Possible clinical consequences
• Constipation
• Anorexia
• Paralytic ileus
• Musculoskeletal pain response
• Muscle spasm
• Impaired muscle function
• Possible clinical consequences
• Immobility
• Weakness and fatigue
• Neurologic
• Impaired cognitive function
• Possible clinical consequences
• Confusion
• Impaired ability to think, reason, and make decisions
• Immunologic
• Decreased immune response
• Possible clinical consequences
• Infection
• Sepsis

Dimensions of pain

• Physiologic
• Genetic, anatomic, and physical determinants of pain influence how painful stimuli are processed, recognized, and described.
• Affective
• Emotional responses to pain such as anger, fear, depression, and anxiety.
• Negative emotions impair patien'ts quality of life.
• Negative link between depression and pain, resuting in impaired function.
• Cognitive
• Beliefs, attitudes, memories, and meaning attributed to pain influence the way in which a person responds to pain.
• Includes pain-related beliefs and cognitive coping strategies used to deal with pain.
• Behavioral
• Observable actions used to express or control pain.
• Examples include facial expressions such as grimacing or irritability.
• People unable to communicate may have behavioral changes (e.g., agitation, combativeness).
• Sociocultural
• Includes demograhics (e.g., age, gender, education, socioeconomic status), support systems, social roles, and culture.
• Age and gender influence nociceptive processes and responses to opioids.
• Families and caregivers influence patient's response to pain through their beliefs and behaviors.
• Culture affects pain expression, medication use, and pain-related beliefs and coping.

Nociception

• The physiologic process by which information about tissue damage is communicated to the central nervous system (CNS).
• Involves four processes:
1. Transduction
2. Transmission
3. Perception
4. Modulation

Transduction

• Involves the conversion of a noxious mechanical, thermal, or chemical stimulus into an electrical signal called an action potential.
• Noxious (tissue damaging) stimuli, including thermal (e.g., sunburn), mechanical (e.g., surgical incision), or chemical stimuli (e.g., toxic substances), cause the release of numerous chemicals such as hydrogen ions, substance P, and adensosine triphosphate (ATP) into the damaged tissues.
• Other chemicals are released from mast cells ( e.g., serotonin, histamine, bradykinin, and prostaglandins) and macrophages (e.g., bradykinin, interleukins, and tumor necrosis factor [TNF])
• These chemicals activate nociceptors, which are specialized receptors or free nerve endings that respond to painful stimuli.
• Activation of nociceptors results in an action potential that is carried from the nociceptors to the spinal cord primarily via small, rapidly conducting, myelinated A-delta fibers and slowly conducting unmyelinated C fibers.

Nociceptors (Transduction)

• In addition to stimulating nociceptors to fire, inflammation and the subsequent release of chemical mediators promote lowered nociceptor thresholds.
• As a result, nociceptors may fire in response to stimuli that previously were insufficient to elicit a response; they may also fire in response to non-noxious stimuli, such as light touch.
• This increased susceptibility to nociceptor activation is called peripheral sensitization.
• Cyclooxygenase (COX), an enzyme produced in the inflammatory response, also plays an important role in peripheral sensitization.
• Leukotrienes, prostaglandins, cytokines, and substance P also are involved in peripheral sensitization.

Nociceptive and neuropathic pain

• Nociceptive pain- The pain produced from activation of peripheral nociceptors
• Neuropathic pain- Pain-related action portentials arising from abnormal processing of stimuli by the nervous system.

Pain medications (Transduction)

• Decreasing the effects of chemicals released at the periphery is the basis of several drug approaches to pain relief.
• NSAIDs, naproxen, and corticosteroids exert their analgesic effects by blocking pain sensitizing chemicals.
• NSAIDs block the action of COX, thereby interfering with the production of prostaglandins.
• Corticosteroids block the action of phospholipase, thereby reducing the production of both prostaglandins and leukotrienes.
• Drugs that stabilize the neuronal membrane and inactivate peripheral sodium channels inhibit production of the nerve impulse. These medications include local anesthetics and antiseizure drugs.

Transmission

• The process by which pain signals are relayed from the periphery to the spinal cord and then to the brain.
• The nerves that carry pain impulses from the periphery to the spinal cord are called primary afferent fibers that include A-delta and C fibers, each of which is responsible for a different pain sensation.
• A-delta fibers are small, myelinated fibers, that conduct pain rapidly and are responsible for the initial, sharp pain that accompanies tissue injury.
• C fibers are small, unmyelinated fibers that trasmit painful stimuli more slowly and produce pain that is typically aching or throbbing in quality.
• Primary afferent fibers terminate in the dorsal horn of the spinal cord, which contains the cell bodies for afferent nerve fibers. Activity in the dorsal horn integrates and modulates pain inputs from the periphery.

Three segments involved in nociceptive signal transmission

1. Transmission along the peripheral nerve fibers to the spinal cord.
2. Dorsal horn processing.
3. Transmission to the thalamus and the cerebral cortex.

Transmission to the spinal cord

• The first-order neuron extends the entire distance from the periphery to the dorsal horn of the spinal cord with no synapses.
• Once generated, an action potential travels all the way to the spinal cord unless itis blocked by a sodium channel inhibitor (e.g., local anesthetic) or disrupted by a lesion at the central terminal of the fiber (e.g., by a dorsal root entry [DREZ] lesion).

Dorsal horn processing (Transmssion)

• Once a nociceptive signal arrives in the CNS, it is processed within the dorsal horn of the spinal cord. Neurotransmitters released from the afferent fiber bind to receptors on nearby cell bodies and dendrites of cells.
• Exogenous and endogenous opioids bind to opioid receptors and block the release of neurotransmitters, particularly substance P.
• Endogenous opioids, which include enkephalin and β-endorphin, are chemicals that are synthesized and secreted by the body. They are capable of producing analgesic effects similar to those exogenous opioids such as morphine.

Central sensitization (Dorsal horn processing)

• Occurs when enhanced excitability occurs in spinal neurons.
• Peripheral tissue damage or nerve injury can cause central sensitization, and continued nociceptive input from the periphery is necessary to maintain it.
• Plays a crucial role in the pathogenesis of chronic pain.
• Defined by an increase in the excitability of neurons within the CNS, so that normal sensory inputs cause abnormal sensing and responses to painful and other stimuli.
• The central processing circuits are disrupted.

C-fiber nociceptors

• With ongoing stimulation of slowly conducting unmyelinated C-fiber nociceptors, firing of specialized dorsal horn neurons gradually increases.
• These inputs create many problems, including the sprouting of wide dynamic range (WDR) neurons and induction of glutamate-dependent N-methyl-D-aspartate (NMDA) receptors.
• When WDR neurons sprout, they grow into areas where pain-receiving nerve cell bodies are located.
• This results in the capacity to transmit a broader range of stimuli-producing signals that are then passed up the spinal cord and brain.
• This process is known as "windup" and is dependent on the activation of NMDA receptor antagonists, such as ketamine (Ketalar), potentially interrupt or block mechanisms that lead to or sustain central sensitization.
• Windup, like central sensitization and hyperalgesia (increased pain responses to noxious stimuli), is induced by C-fiber inputs.

Neuroplasticity (Dorsal horn processing) 

• Refers to an intricate group of processes that allows neurons in the brain to compensate for injury and adjust their responses to new situations or changes in their environment.
• Contributes to adaptive mechanisms for reducing pain but also can result in maladaptive mechanisms that enhance pain.

Central sensitization of the dorsal horn results in

1. Hyperalgesia
2. Painful responses to normally innocuous stimuli (termed allodynia)
3. Prolonged pain after the original noxious stimulus ends (called persistent pain)
4. The extension of tenderness or increased pain sensitivity outside of an area of injury to include uninjured tissue (i.e., referred pain or secondary hyperalsgesia).
• Referred pain must be considered when interpreting the location of pain reported by the person with injury to or disease involving visceral organs.

Transmission to thalamus and cortex

• From the dorsal, nociceptive stimuli are communicated to the third-order neuron, primarily in the thalamus, and several other areas of the brain.
• Fibers of dorsal horn projection cells enter the brain through several pathways, including the spinothalamic tract (STT) and spinoreticular tract (SRT).
• Therapeutic approaches that target pain transmission include opioid analgesics that bind to opioid receptors on primary afferent and dorsal horn neurons. These agents mimic the inhibitory effects of endogenous opioids/

Perception

• Occurs when pain is recognized, defined, and responded to by the individual experiencing the pain.
• In the brain, nociceptive input is perceived as pain.
• Pain perception involves several brain structures.
• The reticular activating system (RAS) is responsible for warning the individual to attend to the pain stimulus.
• The somatosensory system is responsible for localization and characterization of pain.
• The limbic system is responsible for the emotional and behavioral responses to pain.

Modulation

• Involves the activation of descending pathways that exert inhibitory or facilitory effects on the transmission.
• Depending on the type and degree of modulation, nociceptive stimuli may or may not be perceived as pain.
• Can occur at the level of the periphery, spinal cord, brainstem, and cerebral cortex.
• Descending modulatory fibers release chemicals such as serotonin, norepinephrine, GABA, and endogenous opioids that can inhibit pain transmission.

Antidepressant effects through the modulatory system

• Tricyclic antidepressants are used in the management of chronic non-malignant and cancer pain. These agents interfere with the reuptake of serotonin and norepinephrine, thereby increasing their availability to inhibit noxious stimuli.
• Norepinephrine appears to play a greater role in centrally inhibiting pain than does serotonin, which explains why SNRIs have greater analgesic effects than selective serotonin reuptake inhibitors (SSRIs).

Classification of pain

• Pain is categorized as nociceptive or neuropathic based on underlying pathology.
• Pain is also classified as acute or chronic.

Nociceptive pain

• Caused by damage to somatic or visceral tissue
• Somatic pain often is further categorized as superficial or deep.
• Superficial pain arises from skin, mucous membranes, and subcutaneous tissues, and often is described as sharp, burning, or prickly.
• Ex- Sunburn, skin contusions
• Deep pain is often charactierized as deep, aching, or throbbing and originates in bone, joint, muscle, skin, or connective tissue.
• Ex- Arthritis, tendonitis, myofascial pain
• Visceral pain comes from the activation of nociceptors in the internal organs and lining of the body cavities such as the thoracic and abdominal cavities.
• Respond to inflammation, stretching, and ischemia.
• Stretching of hollow viscera in the intestines and bladder that occurs from tumor involvement or obstruction can produce intense cramping pain.
• Ex- appendicitis, pancreatitis, cancer affecting internal organs.
• Generally responsive to nonopioid medications, such as NSAIDs, as well as opioids.

Neuropathic pain

• Caused by damage to peripheral nerves or structures in the CNS. Typically described as numbing, hot-burning, shooting, stabbing, sharp, or electric shock-like in nature, neuropathic pain can be sudden, intense, short-lived, or lingering.
• Paroxysmal firing of injured nerves is responsible for shooting and electric shock-like sensations.
• Common causes include trauma, inflammation (e.g., secondary to hernaited disk inflaming the adjacent nerve and dorsal root ganglion), metabolic diseases (e.g., diabetes mellitus), alcoholism, infections of the nervous system, tumors, toxins, and neurologic diseases.

Deafferentation pain

Sympathetically maintained pain

Poly- and mononeuropathies

• Peripheral polyneuropathies- Pain felt along the distribution of multiple peripheral nerves
• Mononeuropathies- Pain felt along the distiribution of a damaged nerve
• Both arise from damage to peripheral nerves and generate pain that may be described as burning, paroxysmal, or shock-like.
• Ex- postherpetic neuralgia, phantom limb pain, diabetic neuropathies, and trigeminal neuralgia.

Complex regional pain syndrome (CRPS)

• Dramatic changes in the color and temperature of the skin over the affected limb or body part, accompanied by intense burning pain, skin sensitivity, sweating, and swelling.
• Type I is frequently triggered by tissue injury; the term describes all patients with the above symptoms but with no underlying nerve injury.
• Type II is associated with diverse sympathetic dysfunction.
• Neuropathic pain often is not well controlled by opioid analgesics alone. Treatment is typically augmented with adjuvant therapies including tricyclic antidepressants.

Acute pain

• Onset: Sudden
• Duration: Less than 3 months or as long as it takes for normal healing to occur
• Severity: Mild to severe
• Course of pain: Over time and goes away as recovery occurs
• Typical physical and behavioral manifestations: Manifestations reflect sympathetic nervous system activation-
• Increased heart rate
• Increased respiratory rate
• Increased blood pressure
• Diaphoresis/pallor
• Anxiety, agitation, confusion
• Urine retention
• Usual goals of treatment: Pain control with eventual elimination; includes analgesics for symptom control and treatment  of the underlying cause.
• If persists, can lead to disabling chronic pain.
• Sometimes the pain persists and develops into a chronic pan state called postherpetic neuralgia (PHN).

Chronic pain

• Onset- Gradual or sudden
• Duration- Greater than 3 months; may start as acute injury or event but continues past the normal time for recovery
• Severity- Mild to severe
• Cause of pain- May ot be known; original cause of pain may differ from mechanisms that maintain pain
• Course of pain- Typically pain does not go away; characterized by periods of waxing and waning
• Typical physical and behavioral manifestations- Predominantly behavioral manifestations:
• Flat affect
• Decreased physical movement/activity
• Fatigue
• Withdrawal from others and social interaction
• Usual goals of treatment- Pain control to the extent possible; focus on enhancing function and quality of life

Goals of nursing pain assessment

1. Describe the patient's multidimenstional pain experience for the purpose of identifying and implementing appropriate pain management techniques.
2. Identify the patient's goal for therapy and resources for self-management.

Breakthrough pain

• Is transient, moderate to severe pain that occurs in patients whose pain is otherwise well controlled.
• End-of-dose failure is breakthrough pain that occurs before the duration of pain relief that is expected with a specific analgesic.
• Signals the need for changes in the dose of scheduling of the analgesic.

Obtaining information about the location of pain

• Asking the patient to

1. Describe the site(s) of pain.
2. Point to painful areas on the body.
3. Mark painful areas on a pain map.

All pain treatment plans are based on the following principles and practice standards

1. Follow the priniciples of pain assessment.
2. Every patient deserves adequate pain management.
3. Base the treatment plan on the patient's goals.
• Patient's goals for pain treatment should occur at the initial pain assessment.
• Over the course of prolonged therapy, these goals should be reassessed, and progress toward meeting them should be documented.
• The patient determines new goals, however, you may need to work with the patient to establish realistic goals.
4. Use both drug and nondrug therapies.
5. When appropriate, use a multimodal approach to analgesic therapy.
• Multimodal analgesia is the use of two or more classes of analgesic medications to take advantage of the various targets throughout the pain pathways.
• Achieve superior pain relief, enhance patient satisfaction, and decrease adverse effects of individual drugs.
• Has long been an accepted practice for the management of chronic pain and is gaining acceptance in the treatment of acute pain.
6. Address pain using a multidisciplinary approach.
• Multidisciplinary teams frequently include psychology, physical and occupational therapy, pharmacy, spiritual care, and multiple medical specialties such as neurology, pain, palliative care, oncology, surgery, anesthiology.
7. Evaluate the effectiveness of all therapies to ensure that they are meeting the patient's goals.
8. Prevent and/or manage medication side effects.
9. Incorporate patient and caregiver teaching throughout assessment and treatment.
• Content should include information about the cause(s) of the pain, pain assessment methods, treatment goals and options, expectations of pain management, instruction regarding the proper use of drugs, side effect management, and nondrug and self-help pain relief measures.

Managing side effects of pain

• Decreasing the dose of analgesic by 10%-15%
• Changing to a different medication in the same class
• Adding a drug to counteract the adverse effect of the analgesic (e.g., initiatin a bowel regimen using a gentle stimulant laxative and a stool softener for patients experiencing opioid-induced consipation)
• Using an administration route that minimizes drug concentrations at the site of the side effect (e.g., intraspinal administration of opioids is sometimes used to minimize high drug levels that produce sedation, nausea, and vomiting).

Drug therapy for pain

• Pain medications generally are divided into three categories:

1. nonopioids
2. opioids
3. adjuvant drugs

• Mild pain often can be relieved using nonopioids alone. 
• Moderate to severe pain usually requires an opioid.
• Certain types of pain, such as neuropathic pain, often require adjuvant drug therapy alone or in combination with an opioid or another class of analgesics.

Nonopioids

• Include acetaminophen, asprin, and other salicylates, and NSAIDs.
• Characterized by the following:
1. There is an analgesic ceiling to their analgesic properties; that is, increasing the dose beyond an upper limit provides no greater analgesia.
2. They do not produce tolerance or physical dependence.
3. Many are available without a prescription.
• Effective for mild to moderate pain.
• Often used in conjunction with opioids because they allow for effective pain relief using lower opioid doses (thereby causing fewer opioid side effects); this phenomenon is called the opioid sparing effect.

Nonopioids-Aspirin & Acetaminohen

• Effective for ild pain but use is limited by its common side effects, including increased risk for platelet dysfunction and bleeding, especially GI bleeding.
• Acetaminophen has analgesic and antipyretic effects, but unlike aspirin, is has no antiplatelet or antiinflammatory effects.
• Acetaminohen is metabolized by the liver; chronic dosing greater than 4 g/day, acute overdose, or use by patients with severe preexisting liver disease may result in hepatotoxicity.
• Acetaminophen provides multimodal therapy, which is the reason for opioid/acetminophen combinations such as percocet and lortab.

NSAIDs and COX

• Inhibit the enzyme cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostaglandins and related compounds.
• Two forms of the enzyme exist as COX-1 and COX-2.
• COX-1 is found in almost all tissues and is responsible for several protective physiologic functions.
• COX-2 is produced mainly at the sites of tissue injury, where is mediated inflammation.
• Inhibition of COX-1 causes many of the untoward effects of NSAIDs, such as impairment of renal function, bleeding tendencies, GI irritation, and ulceration.
• Inhibition of COX-2 is associated with the therapeutic, antiinflammatory effects of NSAIDs.
• Older NSAIDs, such as ibuprofen, inhibit both forms of COX and are referred to as nonselective NSAIDs.
• NSAIDs that selectively inhibit COX-2 were introduced, which include celecoxib (Celebrex). These are known as COX-2 inhibitors, or "coxibs".
• If NSAIDs are used in patients at risk for GI bleeding, they should have concomitant therapy with a misoprostol (Cytotec) or a proton pump inhibitor (PPI) such as omeprazole (Prilosec). 
• NSAIDs should not be administered concurrently with aspirin as the risk for bleeding and GI adverse events is increased.

Opioids

• Produce their effects by binding to receptors in the CNS.
• This results in

1. Inhibition of the transmission of nociceptive input from the periphery to the spinal cord.
2. Altered limbic system activity
3. Activation of the descending inhibitory pathways that modulate transmission in the spinal cord. Thus opioids act on several nociceptive processes.

Types of opioids

• Are categorized according to their physiologic action (i.e., agonist and antagonist) and binding at specific opioid recepetors (e.g., mu, kappa, and delta).
• The most commonly administered subclass of opioids is the opioid pure agonists, or morphine-like opioids, which bind to mu receptors.
• Opioid agonists are used for both acute and chronic pain.
• Although nociceptive pain appears to be more responsive to opioids than neuropathic pain, opioids are used to treat both types of pain.
• Pure opioid agonists include morphine, oxycodone (Oxycontin), hydrocodone, codeine, methadone, hydromorphone (Dilaudid), oxymorphone (Opana, Opana ER), and levorphanol.
• These drugs are effective for moderate to severe pain because they are potent, have no analgesic ceiling, and can be administered through several routes.

Mixing Opioids

• When opioids are prescribed for moderate pain, they are usually combined with a nonopioid analgesic such as acetaminophen.
• Addition of acetaminophen or NSAIDs limits the total daily dose that can be given.
• Mixed agonist-antagonists bind as agonists on kappa receptors and as weak antagonists or partial agonists on mu receptors. Because of this difference in binding, mixed agonist-antagonists produce less respiratory depression than drugs that act at only mu receptors (mu agonists).
• They also cause more dysphoria and agitation.
• Opioid agonist-antagonists have an analgesic ceiling and can precipitate withdrawal if used in a patient who is physically dependent on mu agonist drugs.
• Partial opioid agonists bind weakly to mu and kappa receptors, which decreases their analgesic efficacy.

Side effects of opioid

• Common side effects of opioids include constipation, nausea and vomiting, sedation, respiratory depression, and pruritus.
• Urinary retention, myoclonus, dizziness, confusion, and hallucinations.
• Constipation is the most common opioid side effect.
• Sedation and respiratory depression are two of the most common fears associated with opioids. Sedation usually is seen in opioid-naive patients in the treatment of acute pain.
• For postoperative patients, the risk for sedation is greatest within 4 hours after leaving the postanesthesia care unit.

Opioids and respiratory depression

• The risk of respiratory depression is also higher in opioid-naive, hospitalized patients who are treated for acute pain.
• Is rare in opioid-tolerant patients and when opioids are titrated to analgesic effect.
• Patients most at risk include those who are elderly, have underlying lung disease or have a history of sleep apnea, or are receiving other CNS depressants.
• For postoperative, the greatest risk opioid-related respiratory adverse events is within the first 24 hours after surgery.
• Clincally significant respiratory depression cannot occur in patients who are awake. Thus the sedation level must be monitored in addition to the respiratory rate.
• Rouse the patient and ask him or her to take deep breaths. Decreasing the opioid dose is also indicated.
• For patients who are excessively sedated or unresponsive, naloxone (Narcan), an opioid antagonist that rapidly reverses the effects of opioids, can be administered.
• Naloxone can be given intravenously or subcutaneously every 2 minutes.
• If the patient has been taking opioids regularly for more than a few days, naloxone should be used judiciously and titrated carefully because it can precipitate severe, agonizing pain, profound withdrawal symptoms, and seizures.

Opioid-induced hyperalgesia (OIH)

• A rare problem with long-term and even short-term use of opioids.
• OIH is a state of nociceptive sensitization caused by exposure to opioids.
• Is characterized by a paradoxic response in which patients actually become more sensitive to certain painful stimuli and report increased pain with opioid use.

Sedation assessment scale

• N= Normal sleep
• 1= Anxious, agitated, or restless
• 2= Calm, cooperative to tranquil (normal baseline without sedation)
• 3= Quiet, drowsy, responds to verbal commands
• 4= Asleep, brisk response to forehead tap or loud verbal stimuli
• 5= Asleep, sluggish response to increasingly vigorous stimuli
• 6= Unresponsive to painful stimuli
• Moderate sedation= Sedation score of 4

Adjuvant analgesic therapy

• These medications comprise classes of drugs that can be used alone or in conjunction with opioid and nonopioid analgesics.
• Were developed for other purposes and found later to be effective for pain.

Corticosteroids

• Used for management of acute and chronic cancer pain, pain secondary to spinal cord compression, and inflammatory joint pain syndromes.
• Are useful when injected epidurally for acute or subacute disk herniations.
• Adverse effects include hypergycemia, fluid retention, dyspepsia and GI bleeding, impaired healing, muscle wasting, osteoporosis, adrenal supression, and susceptibility to infection.
• Because they act through the same final pathway as NSAIDs, corticosteroids should not be given at the same time as NSAIDs.

Antidepressants

• Tricyclic antidepressants (TCA) enhance the descending inhibitory system by preventing the cellular reuptake of serotonin and norepinephrin.
• Higher levels of serotonin and norepinephrine in the synaptic cleft inhibit the transmission of nociceptive signals in the CNS.
• Other potential benefitial actions of TCAs include sodium channel modulation, α1-adrenergic antagonist effects, and a weak NMDA receptor modulation.
• Side effects such as sedation, dry mouth, blurred vision, and weight gain limit their usefulness.

Antiseizure Drugs

• Affect both peripheral nerves and the CNS in several ways, including sodium channel modulation, central calcium modulation, and changes in excitatory amino acids and other receptors.

GABA receptor agonists

• Baclofen (Lioresal), an analog of the inhibitory neurotransmitter GABA, can interfere with the transmission of nociceptive impulses, and is mainly used for muscle spasms.
• Crosses the blood-brain barrier poorly and is much mor effective for spasticity when delivered intrathecally.

α2-Adrenergic agonists

• Are thought to work on the central inhibitory α-adrenergic receptors.
• These agents may also decrease norepinephrine release peripherally.
• They are used for chronic headache and neuropathic pain.

Local anesthetics

• For acute pain from surgery or trauma, can be administered epidurally by continuous infusion, but also by intermittent or continuous infusion with regional nerve blocks.

Mixed mu agonist opioid and NE/5-HT reuptake inhibitors

• Some analgesics have two distinct actions, or dual mechanisms.
• Tramadol (Ultram) is a weak mu agonist and also inhibits the reuptake of norepinephrine and serotonin. Is effective in low back pain, osteoarthritis, diabetic peripheral neuropathic pain, poly neuropathy, and postherpetic neuralgia.
• Most common side effects are similar to those of other opioids, including nausea, constipation, dizziness, and sedation.
• As with other medications that increase serotonin and norepinephrine, this agent should be avoided in patients with a history of seizures because it lowers seizure threshold.

Cannabinoids

• Cannabinoid-derived medications show promise in the treatment of certain pain syndromes and symptomes, but these preparations have sparked considerable controversy, prejudice, and confusion mostly because cannabinoids have some relation to the cannabis plant—also known as marijuana.

Titration

• Analgesic titration is dose adjustment based on assessment of the adequacy of analgesic effect versus the side effects produced.
• There is a wide variability in the amount of analgesic needed to manage pain, and titration is an important strategy in addressing this variability.
• An analgesic can be titrated upward or downward.
• The goal of titration is to use the smallestt dose of analgesic that provides effective pain control with the fewest side effects.

Equianalgesic dosing

• Refers to a dose of one analgesic that is equivalent in pain-relieving effects compared with another analgesic.
• This equivalence permits substitution of analgesics in the event that a particular drug is ineffective or causes intolerable side effects.

Administration routes

• Opioids and other analgesic agents can be delivered via many routes.
• This flexibility allows the health care provider to 
1. target a particular anatomic source of the pain.
2. achieve therapeutic blood levels rapidly when necessary.
3. avoid certain side effects through localized administration.
4. provide analgesia when patients are unable to swallow.

First-pass effect

• Oral opioids are absorbed from the GI tract into the portal circulation and shunted to the liver.
• Partial metabolism in the liver occurs before the drug enters the systemic circulation and becomes available to peripheral receptors or can cross the blood-brain barrier and access CNS opioid receptors, which is necessary to produce analgesia.

Sublingual and buccal routes

• Opioids can be administered under the tongue or held in the mouth and absorbed into the systemic circulation, which would exempt them from the first-pass effect.
• Most of the drug is dissolved in saliva and swallowed, making its metabolism the same as that of oral morphine.

Intranasal route

• Allows delivery of medication to highly vascular mucosa and avoids the first-pass effect.
• Butorphanol (Stadol) is one of the few intranasal analgesics currently available.
• This drug is indicated for acute headache and other intense, recurrent types of pain.
• Intranasal delivery of other opioids is being investigated.

Transdermal route

• Fentanyl (Durgesic) is available as a transdermal patch system for application to nonhairy skin.
• Useful for patients who cannot tolerate oral analgesic drugs.
• Absorption from the patch is slow, and it takes 12 to 17 hours to reach full effect with the first application.
• Transdermal fentanyl is not suitable for rapid dose titration but can be effective if the patient's pain is stable and the dose required to control it is known.
• Patches may need to be changed every 48 hours rather than the recommended 72 hours based on individual responses.
• Creams and lotions are available for joint and muscle pain. It is absorbed locally. 
• This route of administration avoids gastric irritation, but the other side effects of high-dose salicylate are not prevented.

Parenteral routes

• Includes subcutaneous, intramuscular (IM), and intravenous (IV) administration.
• Single, repeated, or continuous dosing (subcutaneous or IV) is possible via parenteral routes.
• IM route is not recommended because injections cause significant pain, result in unreliable absorption, and with chronic use can result in abscesses and fibrosis.
• Onset of analgesia following subcutaneous administration is slow and thus the subcutaneous route rarely is used for acute pain management.

Intraspinal delivery

• epidural or intrathecal opioid therapy involves inserting a catheter into the subarachnoid space (intrathecal delivery) ot the epidural space (epidural delivery).
• Analgesics are injected either by intermittent bolus doses or continuous infusion.
• Percutaneously placed temporary catheters are used for short-term therapy (2 to 4 days), and surgically implanted catheters are used for long-term therapy.
• Although the lumbar region is the most common site of placement, epidural catheters may be placed at any point along the spinal columns.
• Fluoroscopy is used to ensure correct placement of the catheter.

Intraspinal delivery effects

• Intraspinally administered analgesics are highly potent because they are delivered close to the receptors in the spinal cord dorsal horn.
• Nausea, itching, and urinary retention are common side effects of intraspinal opioids.
• A catheter that migrates out of the intrathecal or epidural space will cause a decrease in pain relief with no improvement, even with additional boluses or increases in the infusion rate.
• If an epidural catheter migrates into the subarachnoid space, an increase in side effects will become quickly apparent.
• Confusion, somnolence, and an increased anesthesia (if the infusate contains an anesthetic) occur.
• Correct placement of an intrathecal catheter can be checked by aspirating cerebrospinal fluid (CSF).
• Migration of a catheter in a blood vessel may cause an increase in side effects because of systemic drug distribution.
• Acute bacterial infection (meningitis) is manifested by photophobia, neck stiffness, fever, headache, and altered mental status.

Implantable pumps

• Intraspinal catheters can be surgically implanted for long-term pain relief.
• The surgical placement of an intrathecal catheter to a subcutaneously place pump and reservoir allows for the delivery of drugs directly into the intrathecal space.
• Changes are made by reprogramming the pump or changing the mixture or concentration of drug in the reservoir.
• The pump is refilled every 30 to 90 days depending on flow-rate, mixture, and reservoir size.

Patient controlled analgesia (PCA)

• A specific type of IV delivery system.
• Can also be connected to an epidural catheter (patient-controlled epidural analgesia [PCEA]).

Patient controlled analgesia (PCA)

• A specific type of IV delivery system.
• Can also be connected to an epidural catheter (patient-controlled epidural analgesia [PCEA]).

Therapeutic nerve block

• Generally involve one-time or continuous infusion of local anesthetics into a partiular area to produce pain relief.
• These techniqus are also called regional anesthesia.
• Nerve blocks interrupt all afferent and efferent transmission to the area, and thus are not specific to nociceptive pathways.
• They include local infiltration of anesthetics into a surgical area and injection of anesthetic into a specific nerve or nerve plexus.
• Nerve blocks often are used during and after surgery to manage pain.
• For longer-term relief of chronic pain syndromes, local anesthetics can be administered via a continuous infusion.
• Adverse effects include dysrhythmias, confusion, nausea and vomiting, blurred vision, tinnitus, and metalic taste.
• Temporary nerve blocks affect both motor function and sensation and typically last 2 to 24 hours depending on the agent and site of injection.
• Motor ability generally returns before sensation.

Neuroblative techniques

• Neuroblative interventions are performed for severe pain that is unresponsive to all other therapies.
• Destroy nerves, thereby interrupting pain transmission.
• Destruction is accomplished by surgical resection or thermocoagulation, including radiofrequency coagulation.
• Neuroblative interventions that destroy the sensory division of a peripheral or spinal nerve are classified as neurectomies, rhizotomies, and sympathectomies.
• Neurosurgical procedures that abate the lateral spinothalamic tract are classified as cordotomies if the tract is interrupted in the spinal cord, or tractotomies if the interruption is in the medulla or the midbrain of the brainstem.

Neuroaugmentation

• Involves electrical stimulation of the brain and the spinal cord.
• Spinal cord stimulation (SCS) is performed much more often than deep brain stimulation.
• The most common use of SCS is for chronic back pain secndary to nerve damage that is unresponsive to other therapies.
• Other uses include complex regional pain syndrome, spinal cord injury pain, and interstitial cystitis.
• Potential complications include those related to the surgery, migration of the generator, and nerve damage.

Massage

• Used for acute and chronic pain.
• Superficial massage- Movement of the hands or fingers over the skin slowly or briskly with long strokes or in circles.
• Deep massage- Applying firm pressure to the skin to maintain contact while massaging the underlying tissues.
• Trigger point- A circumscribed hypersensitive area within a tight band of muscle.
• Is caused by acute or chronic muscle strain and can often be felt as a tight knot under the skin.
• Is performed either by applying strong, sustained digital pressure, deep massage, or gentler massage with ice followed by muscle heating.

Exercise

• For patients with chronic pain, particularly those with musculoskeletal pain.
• Enhances circulation and cardiovascular fitness, reduces edema, increases muscle strength and flexibility, and enhances physical and psychological functioning.
• Include aerobic exercise, stretching, and strengthening exercises.

Transcutaneous electrical nerve stimulation (TENS)

• Involves the delivery of an electric current through electrodes applied to the skin surface over the painful region, at trigger points, or over a peripheral nerve.
• Consists of two or more electrodes connected by lead wires to a small, battery-operated stimulator.
• May be used for acute pain, including postoperative pain and pain associated with physical trauma.
• May be effective for some chronic pain patients.

Heat therapy

• Superficial heat can be applied using an electric heating pad (dry or moist), a hot pack, hot moist compresses, warm wax (paraffin), or a hot water bottle.
• For exposure to large areas of the body, patients can immerse themselves in a hot bath, shower, or whirlpool.

Cold therapy

• Dry cold can be applied by means of an ice bag.
• Moist cold can be applied by means of towels soaked in ice water, cold hyrdocollator packs, or immersion in a bath or under running cold water.
• Cold therapy is believed to be more effective than heat for a variety of painful conditions, including acute pain from trauma or surgery, acute flare-ups of arthritis, muscle spasms, and headache.

Nondrug therapies for pain

• Physical therapies
• Acupuncture
• Application of heat and cold
• Exercise
• Massage
• Transcutaneous electrical nerve stimulation (TENS)
• Cognitive therapies
• Distraction
• Hypnosis
• Imagery
• Relaxation strategies
• Relaxation breathing
• Imagery
• Meditation
• Art therapy
• Music therapy

Heat and cold therapy teaching

• Heat
• Do not use heat on an area that is being treated with radiation therapy, is bleeding, has decreased sensation, or has been injured in the past 24 hours.
• Do not use any menthol-containing products (e.g., Ben-Gay, Vicks, Icy Hot) with heat applications because this may cause burns.
• Cover the heat source with a towel or cloth before applying to the skin to prevent burns.
• Cold
• Cover the cold source with a cloth or towel before applying to the skin to prevent tissue damage.
• Do not apply cold to areas that are being treated with radiation therapy, have open wounds, or have poor circulation.
• If it is not possible to apply the cold directly to the site, try applying it right above or below the painful site or on the opposite side of the body on th corresponding side (e.g., left elbow if the right elbow hurts).

Opioid rotation

• Involves switching from one opioid to another, assuming that the new opioid will be more effective lower equianalgesic doses.
• Very high opioid doses can result in hyperalgesia rather than pain relief.
• Thus further increase in the dose can lead to higher pain levels.

Manifestations of withdrawal syndrome from short-acting opioids

• Psychosocial secretions
• Early response (6-12 hr)
• Anxiety
• Lacrimation
• Rhinorrhea
• Diaphoresis
• Late response (48-72 hr)
• Excitation 
• Diarrhea
• Other
• Early response (6-12 hr)
• Yawning
• Piloerection
• Shaking chills
• Dilated pupils
• Anorexia
• Tremor
• Late response (48-72 hr)
• Restlessness
• Fever
• Nausea an vomiting
• Abdominal cramping pain
• Hypertension
• Tachycardia
• Insomnia

Under the standards, health care facilities are required to

1. recognize the patient's right to appropriate assessment and management of pain.
2. identify pain in patients during their initial assessment and as needed, during ongoing, periodic reassessments.
3. Educate health care providers about pain assessments and management and ensure competency.
4. Educate patients and their families about pain management.

Assissted suicide

• Currently Oregon and Washington are the only states in the US where assissted suicide is legal.

Treatment of pain in elderly

• Older adults metabolize drugs more slowly than younger patients and thus are at greater risk for higher blood levels and adverse effects. For this reason, the adage "start low and go slow" needs to be applied to analgesic therapy in this age group.
• The use of NSAIDs in the elderly is associated with a high frequency of serious GI bleeding. For this reason, acetaminophen should be used whenever possible.
• Older adults often are taking many drugs for one or more chronic conditions. The addition of analgesics can result in dangerous drug interactions and increased side effects.
• Cognitive impairment and ataxia can be exacerbated when analgesics such as opioids, antidepressants, and antiseizure drugs are used. This requires that health care providers titrate drugs slowly and monitor carefully for side effects.

Assessing pain in nonverbal patients

1. Obtain a self-report when possible (never assume a person is unable to give verbal report).
2. Investigate potential causes of pain.
3. Observe patient behaviors that indicate pain (e.g., grimacing, frowning, rubbing a painful area, groaning, and restlessness).
4. Obtain surrogate reports of pain from professional and family caregivers.
5. Try to use analgesics and reassess the patient to observe for a decrease in pain-related behaviors.