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PAIN

Joint Pain

Nociception

Nociceptive perception: Pain an obnoxious experience, has sensory and behavioral components with modulation of the sensory nociceptive experience subserved at various CNS levels and by various neural components.

  • Most of the somatosensory modalities are primarily informative, whereas pain is a protective modality.

  • Pain differs from the classical senses (hearing, smell, taste, hearing, vision) because it has both discriminative sensation and a graded emotional experiences associated with actual or potential tissue loss.

  • Pain is termed nociceptive (nocer-to hurt in Latin) and nociceptive means sensitivity to noxious stimuli. Noxious stimuli are the ones that cause tissue damage and activate pain receptors.

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Nociceptors

Bare nerve endings act as nociceptors in the skin, intramuscular connective tissue, blood vessels, periosteum, and most thoracic and abdominal viscera. Principle stimuli for activation are mechanical, thermal, and chemical.

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  • Nociceptors are ramifications of finely myelinated and unmyelinated afferent axons. Most common nociceptors are the bare nerve endings. Cutaneous nociceptors include:

    • High-threshold mechanical nociceptors (HTM's) associated with small myelinated axons (A-Delta fibers),

    • Myelinated mechanothermal nociceptors (MTs) (A-delta fibers)

    • Polymodal nociceptors associated with unmyelinated fibers.

    • HTM's respond only to intense mechanical stimuli, with a threshold much higher than non-nociceptive mechanoreceptors.

Pain Fibers

  • Afferent fibers that convey nociception are small myelinated fibers (A Delta, CV 5-30 m per second) and unmyelinated axons (C fibers, CV 0.5 - 2 m per second). Nociceptor afferents count for 10% of myelinated fibers and 90% of the unmyelinated fibers.

  • A-delta fibers (group III fibers) are 2-5 mm in diameter, myelinated, have a fast conduction velocity (5-40 meters/sec), and carry information mainly from the nociceptive-mechanical or mechanothermal-specific nociceptors. Their receptive fields are small. Therefore, they provide precise localization of pain.

  • C-fibers (group IV fibers) are 0.4-1.2 mm in diameter, unmyelinated, have a slow conduction velocity (0.5-2.0 meters/sec), and are activated by a variety of high-intensity mechanical, chemical and thermal stimulation and carry information from polymodal nociceptors. C-fibers comprise about 70% of all the fibers carrying noxious input.

 

Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect damage. They transduce various noxious stimuli into receptor potentials, initiating an action potential in the pain nerve fibers. This action potential is transmitted to the spinal cord, making a synaptic connection in lamina I and/or II. The cell bodies of nociceptors are mainly in the dorsal root and trigeminal ganglia. No nociceptors are found inside the CNS.

Types of Nociception

Silent Nociceptors

  • There are silent (sleep) nociceptors in the skin and deep tissue. Normally unresponsive, they become awakened to mechanical stimulation during inflammation and tissue injury.

  • One possible explanation of the "awakening" phenomenon is that continuous stimulation from the damaged tissue reduces the threshold of these nociceptors and causes them to begin to respond.

  • This activation of silent nociceptors may contribute to the induction of hyperalgesia, central sensitization, and allodynia (see below). Many visceral nociceptors are silent nociceptors.

 

Hyperalgesia

  • Extreme sensitivity  to a noxious stimulation is called hyperalgesia.

  • Reduced pain threshold in the inflamed area, activation of silent nociceptors, and tissue damage eliciting prolonged nerve stimulation are thought to elicit hyperalgesia. The result is amplification and persistence of pain.

  • The reddened skin surrounding a pinprick is an area of hyperalgesia

 

Allodynia

  • Nonpainful stimulus eliciting pain is known as allodynia, for example, touch to sunburned skin.

  • Lowering of the pain threshold and rerouting of the damaged neuronal connections to sensory receptors (i.e., touch-sensitive fibers reroute and make a synaptic connection into areas of the spinal cord that receive input from nociceptors) are two explanations behind allodynia

 

Double pain sensations

  • Two sequential pain sensations in short time intervals are the result of sudden painful stimulation.

  • The first one is immediately after the damage, followed several seconds later with additional pain sensation.

  • Several seconds difference in perception is because a fast transmitting sensation carried via A-delta fibers and followed several seconds later with slow transmitting pain information carried via C-fibers.

Deep Somatic Versus Visceral Pain

Deep Somatic pain: muscle, tendons, fascia, joints, and periosteum. Largely free nerve endings associated with A-delta and C-fibers. Deep aching pain, and not well-localized as cutaneous pain.

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Visceral pain: Many visceral organs afferents do not serve a sensory function but rather are involved with reflex autonomic regulation. There is a lack of sensation other than pain when stimulated. The intestine is relatively insensitive to direct tissue damage such as burning or cutting. Stimulation produces a poorly localizing aching or spasmodic, cramping pain.

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Referred pain: Visceral pain is accompanied by the perception of pain arising in a somatic structure that shares the same spinal level of innervation.

Reaction to Somatic Pain

 Three responses follow sudden, unexpected damage to the skin:

  1. Startle response. This is a complex psychosomatic response to a sudden, unexpected stimulus, which includes A flexion reflex, postural readjustment, and orientation of the head and eyes to examine the damaged area.

  2. Autonomic response. This response includes NE and E release, ACTH and/or cortisol release, and vasoconstriction and piloerection.

  3. Behavioral response. This response includes Vocalization, rubbing designed to diminish pain, learning to respond to sudden pain and psychosomatic pain.

Central Pain Pathways

In simple terms, the information about pain travels through different paths in the spinal cord and brain:

  1. Dorsal Horn and Central Projections:

    • Information about pain and other sensations comes through dorsal roots to specific layers in the dorsal horn of the spinal cord.

    • Different types of nerve fibers bring different types of information, like A-delta fibers for certain sensations and sympathetic fibers for visceral (organ-related) sensations.

    • Chemicals like excitatory amino acids and substances like substance P play a role in transmitting these signals.

  2. Neospinothalamic Tract:

    • Some spinal cells specifically respond to strong, unpleasant stimuli (noxious stimuli).

    • These neurons connect to a pathway called the neospinothalamic tract, which carries information to the brain, including areas related to emotions.

    • This tract helps us recognize and locate pain.

  3. Paleospinothalamic Pathway:

    • Most pain-sensing neurons make connections in specific layers of the spinal cord.

    • These neurons have different tracts, such as spinoreticular and spinotectal, which reach various brain regions, including the thalamus.

    • The thalamus is crucial for processing sensory information.

  4. Archispinothalamic Pathway:

    • This is an older pathway that carries noxious (painful) information.

    • It travels through various brain areas, including the thalamus and limbic system, which is associated with emotions.

    • The brain's reaction to pain involves regions like the cingulate gyrus, somatosensory cortex, and more.

In essence, these pathways help our brain understand, locate, and react to different types of pain, involving both the physical sensation and the emotional response.

Central modulation of Nociception

In simpler terms, pain regulation involves both peripheral (around the nerves) and central (in the brain and spinal cord) mechanisms:

  1. Peripheral Mechanisms:

    • Nociceptors (pain receptors) can become more sensitive due to factors like heat or chemicals, known as sensitization.

    • Local circuits and signals from the brain can change how pain signals are sent through the spinal cord.

  2. Central Mechanisms:

    • Cells in specific layers of the spinal cord can modulate pain signals locally (intra) and between segments (inter).

    • Natural painkillers in the body, called endogenous opioids, play a key role in reducing pain. Opioid receptors on nerve endings are important for the action of opioid pain relievers.

    • Descending pathways from the brain, like the periaqueductal gray (PAG) in the midbrain and the Nucleus Raphe Magnus (NRM) in the medulla, use substances like serotonin and norepinephrine to inhibit pain signals in the spinal cord.

  3. Supraspinal Sites:

    • Areas like the somatosensory cortex (part of the brain) and certain parts of the hypothalamus can provide temporary pain relief by stimulating the spinal cord through the corticospinal tract.

  4. Balance in Pain Control:

    • The balance between inhibiting (reducing) and facilitating (increasing) pain control systems in the body determines how pain is perceived.

    • Chronic pain conditions may arise from an imbalance in these control systems.

In summary, the body has intricate mechanisms to regulate and control pain, involving both local circuits in the spinal cord and signals from higher brain regions. The balance between these systems influences how we experience and cope with pain.

Endogenous opioids and opioid receptors

Our bodies have natural substances called opioids that help relieve pain. There are three types: enkephalins, dynorphins, and endorphins. They share a common starting sequence of amino acids. These opioids come from different genes and are concentrated in specific parts of the brain and spinal cord.

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Our body has special receptors for these opioids, called mu, kappa, and delta. These receptors are like switches connected to proteins. When activated, they control channels that affect potassium and calcium, helping regulate pain.

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Mu receptors, found mainly in the brain and spinal cord, respond well to morphine. The strength of painkillers like morphine depends on how well they connect to mu receptors. Kappa receptors, located in the spinal cord and brainstem, play a role in controlling how we feel pain. These receptors, along with the opioids that connect to them, help explain how our bodies naturally manage pain.

Pain Mechanisms

The sensation of pain is caused by the activation of nociceptors when there is tissue injury. There are two main types of pain: nociceptive pain and neuropathic pain.

Nociceptive Pain:

  • Acute Nociceptive Pain: Caused by tissue injury, it can be either somatic or visceral.

    • Somatic Pain: Clearly localized, sharp, or dull.

    • Visceral Pain: Less localized, felt as crampy, spasmodic, or aching. Often associated with referred pain.

  • Chronic Nociceptive Pain: Similar in character to acute pain, but long-lasting. It involves the modulation of nociceptive transmission and affects emotions. Can lead to conditions like depression, sleep disorders, and physical consequences such as disuse-related issues (deconditioning, muscle atrophy, joint immobility).

Neuropathic and Deafferentation Pain:

  • Results from peripheral nerve injuries, including nerve root compression, nerve transection, neuritis (inflammation), and polyneuropathies.

  • Characterized by sharp, lancinating pain that is intense and brief, or shock-like and well-localized. Often follows a dermatomal or peripheral nerve distribution.

  • Mechanisms include the activation of normal nociceptors in a nerve (nervi nervorum), spontaneous or induced discharges in injured nociceptor afferents, deafferentation with central pain generation, and activation of sensitized mechanoreceptors by efferent sympathetic activity (sympathetically maintained pain).

  • Nociceptors in perineural and epineural tissue contribute to nerve root impingement and peripheral nerve pain.

  • Disorders like diabetes and amyloidosis can selectively affect small afferent fibers, leading to abnormal activity and neuropathic pain.

  • Central pain generation involves abnormal activity in central pathways, changes in neurotransmitter function, receptor sensitivity, and alterations in descending pathways. It is diffuse, less well-defined, and less likely to be lancinating.

  • Similarities between peripheral and central induced pain include distribution in a region of tactile imperception, tactile input taking on a painful quality disproportionate to stimulus intensity (hyperpathia), and the addition of a highly emotive burning quality to the perceived pain.

  • Tricyclics and anticonvulsants can relieve both types of deafferentation pain, and efferent peripheral nervous system activity may contribute to chronic neuropathic pain syndromes. Ephapsis (abnormal activation of peripheral neurons by electrical coupling) is observed in animal models but is not well understood in humans.

Complex Regional Pain Syndrome (CRPS)

Definition: CRPS is a condition affecting the sympathetic nervous system, either in the central nervous system or in response to body events.

Onset and Demographics:

  • Typically begins in the limbs, commonly starting in the hands.

  • More prevalent in women; onset often occurs in early to mid-adulthood.

Symptoms and Progression:

  • Initial symptoms include swelling, color and temperature changes, atrophy, and loss of limb function.

  • Pain starts distally, feeling like burning and becoming more sensitive over time (allodynia).

  • Pain progresses upwards and intensifies with activity or lowering the limb.

Physical Signs:

  • Observable signs include edema, temperature fluctuations, increased sweating, and alterations in skin, muscles, and bone.

Treatment Approaches:

  • Blocking sympathetic activity, via drugs or surgery, is a common method for pain relief.

  • Studies indicate variable success, and placebo effects are comparable.

Chronic Changes in CRPS:

  • Glossy skin, fat loss, and nail changes.

  • Bone demineralization visible in hand X-rays.

  • Reduced range of motion.

  • Muscle atrophy and weakness.

  • Unusual hand postures, affecting half of patients (contractures or dystonia).

  • Progression to sensory loss (anesthesia dolorosa) and heightened pain sensitivity (hyperalgesia).

Central Nervous System Involvement:

  • CRPS-related changes are associated with significant alterations in the central nervous system.

Challenges in Treatment:

  • Sympathetic blockade trials are suggested but often show limited long-term effectiveness.

  • Comprehensive management involves medical, physical, and psychological therapies.

  • Pain severity tends to decrease over time in many cases.

Idiopathic and Psychogenic Pain.

Understanding Pain Without Clear Physical Cause:

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Pain without a clear physical cause, known as idiopathic or psychogenic pain, is often related to emotional and psychological factors. Many individuals with chronic pain experience symptoms that are linked to stress, anxiety, and daily life challenges. Conditions like tension headaches and fibromyalgia fall into this category. When emotional tension and fatigue play a significant role in pain complaints, psychogenic factors are suspected.

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Identifying Psychological Factors:

  • Patients with anxiety disorders or certain personality traits may experience somatization, where emotional issues manifest as physical pain.

  • Conversion disorders, often involving headaches, are common in individuals with obsessive or certain personality traits. Chronic use of painkillers may not be beneficial and can sometimes worsen the problem.

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Depression and Pain:

  • Features of depression are common in those with chronic pain syndromes, amplifying the severity of pain.

  • Headaches are a prevalent complaint in depression, with major depression present in 5-10% of chronic pain patients and 50% of those with mild affective disorder.

  • Schizophrenic patients rarely report pain as a primary concern, though chronic headaches are common.

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Malingering and Secondary Gain:

  • Malingering involves feigning illness, like chronic pain, for personal benefit.

  • Patients who malinger often exaggerate symptoms and resist cooperation during exams or treatment efforts.

  • While uncommon, malingering should be considered only after excluding other diagnoses in chronic pain patients.

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Psychological Influence on Nociceptive Pain:

  • Psychological factors, especially anxiety, strongly influence nociceptive pain.

  • The overlap between central pain mechanisms and emotive mechanisms, particularly involving the opioid and aminergic systems, plays a crucial role in the production of psychogenic pain.

Approach to Patients with Pain

Key Aspects of Successful Pain Management:

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1. Categorization of Pain:

  • Successful pain management begins with characterizing pain as nociceptive, neuropathic, psychogenic, or a combination.

  • This categorization guides subsequent evaluations and helps determine appropriate therapies.

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2. Acute Pain:

  • Discerning features of acute pain include location, character, mode of onset, aggravating or relieving factors, and associated symptoms like fever or nausea.

  • Radiating pain may suggest referred or neuropathic origins.

  • Assessments during the interview should include pain severity, emotional response, and attributable factors. Trusting the patient's report is crucial unless strong evidence suggests otherwise.

  • Examination involves searching for signs of inflammation, tenderness, swelling, and signs of irritation in various body systems.

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3. Understanding Pain Causes:

  • Identifying the cause and mechanism is essential for developing an effective treatment plan.

  • Symptomatic treatment without identifying the cause can lead to permanent tissue damage.

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4. Self-Limited and Mild Pain:

  • Some pains with a self-limited and mild nature are considered part of normal sensations.

  • Issues like analgesic rebound headaches may arise when mild analgesics are overused, perpetuating the problem.

  • Unexplained pain complaints alongside medical illnesses require thorough exclusion of other causes.

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5. Chronic Pain:

  • Chronic pain, lasting for months without a clear cause and significantly affecting normal activities, is challenging.

  • Conditions like reflex sympathetic dystrophy (RSD) may lead to chronic incapacitating pain after minor trauma.

  • Certain CNS disorders can cause chronic pain syndrome, but many chronic pain patients lack a clear CNS disturbance.

  • Psychological factors are predominant in such cases, necessitating a multidisciplinary approach involving pharmacological, behavioral, and psychological interventions.

PHARMACOLOGICAL APPROACHES TO PAIN MANAGEMENT

Pain Management Approaches

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1. WHO's Analgesic Approach:

  • Recommended for patients with persistent somatic nociceptive pain.

  • Emphasizes titration of analgesics based on pain severity, regular dosing, and use of non-analgesic adjuvant medications.

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2. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs):

  • Initial use for pain.

  • Progression to low-potency opioids and adjuvants.

  • Advancement to more potent opioids if needed.

  • Specialized routes (IM, IV, epidural) for specific situations.

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3. Placebo Effect:

  • Contributes to pain relief in various treatments.

  • About 30% of patients respond to placebos in trials.

  • Response is not exclusive to psychogenic or nociceptive pain.

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4. Nonopioid Analgesics:

  • Includes acetaminophen and NSAIDs.

  • Effective for mild-to-moderate nociceptive pain.

  • NSAIDs have analgesic, anti-inflammatory, and antipyretic properties.

  • Duration and properties vary among different medications.

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5. Opioid Analgesics:

  • Mild opioids (codeine, oxycodone) for mild pain.

  • Strong opioids (morphine, hydromorphone) for severe pain.

  • Consideration of side effects, tolerance, and potential dependence.

  • Physical and psychological dependence are distinct phenomena.

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6. Pain Management Strategies:

  • Individualized treatment based on pain type and severity.

  • Around-the-clock dosing for persistent pain.

  • Escalation until pain control or toxicity, without a ceiling effect.

  • Parenteral titration for severe pain, especially in certain situations.

  • Use of adjuvant medications, like anticonvulsants and tricyclic antidepressants, to enhance analgesia.

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7. Additional Approaches:

  • Corticosteroids for short-term use in specific conditions.

  • Capsaicin for refractory postherpetic neuralgia.

  • Other adjuvants like stimulants, benzodiazepines, and neuroleptics.

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8. Caution and Individualization:

  • Careful consideration of side effects, tolerance, and dependence.

  • Multidisciplinary approach with various medications for comprehensive pain management.

  • Regular assessment and adjustments to ensure effectiveness and minimize risks.

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Paraminophenol Derivatives

Acetaminophen

Salicylates

Aspirin

Diflunisal (Dolobid)

Choline magnesium trisalicylate (Trilisate)

Propionin acids

Ibuprofen

Naproxen

Acetic Acids

Indomathecin

Sulindac

Ketorolac

Enolic acid

Piroxicam

Fenamic acid

Mefenamic acid

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  1. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

    • Propionic acids (e.g., ibuprofen) and acetic acids (e.g., naproxen) inhibit cyclo-oxygenase for pain relief.

    • Unlike aspirin, their cyclo-oxygenase inhibition is reversible.

    • Propionic acids have minimal interaction with warfarin.

    • Uncommon side effects include renal toxicity and aseptic meningitis.

  2. Acetic Acids

    • Indomethacin and sulindac, used for chronic arthritis.

    • Ketorolac is a potent NSAID with a risk of gastric ulceration.

    • Piroxicam, with aspirin-like potency, is taken once a day due to its prolonged half-life.

  3. Chronic Pain Management

    • Sulindac, naproxen, or piroxicam are chosen for chronic pain, with a 2-week trial for assessment.

    • If one NSAID doesn't work, another class is tried.

  4. Opioid Analgesics

    • Mild opioids: Codeine, oxycodone, hydrocodone.

      • Codeine for mild to moderate pain, but it can cause nausea.

    • Strong opioids: Morphine, hydromorphone, fentanyl.

      • Potent but may cause constipation and dysphoria.

      • Physical and psychological dependence risks, especially in those with a history of drug abuse.

  5. Chronic Opioid Therapy

    • Starts with short-acting opioids, with dosage escalation until pain control or toxicity.

    • No ceiling effect, and high doses can be tolerated.

    • Parenteral titration for severe pain, and radiotherapy can reduce analgesic needs.

  6. Adjuvant Medications in Pain Management

    • Anticonvulsants, tricyclic antidepressants, benzodiazepines, stimulants, corticosteroids, capsaicin, etc.

    • Used to enhance analgesic effects and reduce opioid dosage and dependence.

  7. Monitoring and Adjustment

    • Crucial to monitor and adjust pain management strategies based on individual patient responses and needs.

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1. Strong Opioids:

  • Morphine:

    • Half-life: 2-3 hours.

    • Dosage: 2-10 mg IM/IV, 30-60 mg PO q4h.

    • MS Contin: Sustained-release form with an 8-12 hour duration.

  • Hydromorphone (Dilaudid):

    • Half-life: 2-3 hours.

    • Dosage: 1-4 mg PO q4h.

    • High potency and short half-life make it suitable for chronic therapy.

  • Pentazocine (Talwin):

    • Half-life: 2-3 hours.

    • Dosage: 50-100 mg PO q4h.

    • Mixed agonist and antagonist, with a ceiling effect on analgesia.

    • May precipitate withdrawal in opioid-dependent patients.

  • Methadone (Dolophine):

    • Half-life: 15-30 hrs.

    • Dosage: 10-20 mg PO q4h.

    • Variable duration of analgesia (4-8 hours), long half-life leads to drug accumulation and prolonged CNS toxicity.

  • Levorphanol (Levo-Dromoran):

    • Half-life: 12-16 hrs.

    • Dosage: 2-4 mg PO q4h.

    • Side effects similar to methadone.

  • Fentanyl Transdermal (Duragesic):

    • Half-life: 3-12 hrs.

    • Dosage: 25-100 microgram/hr transdermal patch every 3 days.

    • Extremely potent, slow titration recommended.

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2. Opioid Use and Dependence:

  • Codeine:

    • Mild analgesic with a duration of action of 2-4 hours.

    • Used for mild to moderate pain when NSAIDs are ineffective.

    • Common side effects include nausea, constipation, and dysphoria.

  • Morphine and Hydromorphone:

    • Prototypes of high-potency opioids with rapid onset and short duration.

    • Sustained-release formulations like MS Contin for prolonged action.

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  • Physical Dependence:

    • Develops with chronic opioid use, leading to withdrawal symptoms.

    • Severity varies based on opioid potency and half-life.

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  • Psychological Dependence:

    • Concern for addiction-related behavior, especially in those with a history of drug abuse.

    • Risk varies with pain type (nociceptive, neuropathic, idiopathic, or psychogenic).

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3. Chronic Opioid Therapy and Pain Management:

  • Chronic Therapy:

    • Initiates with short-acting opioids, adjusted based on patient response.

    • "Around-the-clock" dosing for persistent and chronic pain.

    • Opioid titration achieved in hours to days.

  • Parenteral Titration:

    • Rapid titration for severe pain or patients intolerant to oral medications.

    • Preferable options: Morphine or hydromorphone.

  • Switching to Long-Acting Opioids:

    • Methadone recommended for moderate to high doses, titrated slowly to avoid sedation.

  • Transdermal Fentanyl:

    • Effective for continuous chronic opioid therapy with delayed onset.

    • Requires short-acting opioids for breakthrough pain.

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4. Adjuvant Medications in Pain Management:

  • Used in Conjunction:

    • Opioids and NSAIDs complement each other, reducing opioid dosage and dependence.

    • Anticonvulsants, Tricyclic Antidepressants, Benzodiazepines, Stimulants, Corticosteroids, Capsaicin, and Others:

    • Employed to enhance analgesic effects and address specific pain conditions.

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5. Monitoring and Adjustment:

  • Crucial:

    • Regular monitoring and adjustment of pain management strategies based on individual responses and needs.

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Intrathecal or Epidural Approaches:

  • Limited use for patients with lower extremity or pelvic pain.

  • May decrease systemic opioid circulation but not always.

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Conclusion: A comprehensive approach to pain management involves understanding opioid characteristics, addressing dependence concerns, utilizing adjuvant medications, and constantly adjusting strategies to meet individual patient needs.

 

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Summary: Opioid Administration and Adjuvant Medications in Pain Management

1. Opioid Administration:

  • Initial Choice:

    • Short-acting mild opioids (codeine or oxycodone with acetaminophen) on a 4-6 hour schedule.

    • Effective for acute or persistent pain of mild to moderate severity.

  • Chronic Pain Management:

    • "Around-the-clock" dosing for persistent and chronic pain.

    • Supplemental doses for breakthrough pain.

  • Titration and Dose Escalation:

    • Opioid titration achieved in hours to days.

    • Increment of less than 25% seldom improves pain in chronic opioid therapy.

    • Larger increments may lead to nausea, dysphoria, or sedation.

    • No ceiling effect; opioids can be tolerated in high doses.

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2. Parenteral Titration:

  • Rapid Titration:

    • Parenteral titration for severe pain or patients intolerant to oral medications.

    • Preferable options: Morphine or hydromorphone.

  • Continuous Infusion:

    • Continuous infusion advantages in terms of toxicity and efficacy.

  • Switching Opioids:

    • Incomplete cross-tolerance between opioids.

    • Switching requires a 25-50% decrease in the newly calculated dose.

  • Breakthrough Pain:

    • As-needed boluses for breakthrough pain, often via patient-controlled delivery pump.

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3. Other Pain Management Strategies:

  • Radiotherapy:

    • Reduces the need for analgesics in painful metastasis.

  • Long-Acting Opioids (e.g., Methadone):

    • Recommended for patients requiring moderate to high doses.

    • Slow titration to avoid high steady-state levels and prolonged sedation.

  • MS Contin:

    • Sustained-release oral morphine for stable serum levels.

    • Supplemented with standard oral morphine as needed.

  • Transdermal Fentanyl:

    • Delivers 25-100 micrograms per hour for 2-3 days.

    • Delayed onset due to the reservoir effect; titration over several days.

  • Autonomic and CNS Effects:

    • Dose-limiting with increasing opioid dosage, particularly in CNS metastasis.

    • Switching to equally potent opioids with a modest decrease in dosage for intolerant patients.

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4. Adjuvant Medications in Pain Management:

  • Anticonvulsants (e.g., Phenytoin, Gabapentin):

    • Used for neuropathic pain, postherpetic pain, and trigeminal neuralgia.

  • Tricyclic Antidepressants (e.g., Amitriptyline):

    • Monotherapy for neuropathic pain and in conjunction with other analgesics for nociceptive pain.

  • Benzodiazepines and Baclofen:

    • Diazepam for spasticity; Baclofen for trigeminal neuralgia and refractory neuropathic pain.

  • Stimulants (e.g., Dextroamphetamine):

    • Enhance morphine-induced analgesia and reduce sedation.

  • Corticosteroids:

    • Limited for short-term use as adjuvants in controlling pain caused by various conditions.

  • Capsaicin:

    • Topical application for refractory postherpetic neuralgia.

  • Other Agents:

    • Mexiletine (anesthetics and antiarrhythmic).

    • Fluphenazine (neuroleptics).

    • Clonidine (alpha-adrenergic agents).

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Conclusion: A multimodal approach combining opioids with adjuvant medications and employing various administration methods provides a comprehensive strategy for effective pain management, tailored to individual patient needs and conditions. Regular monitoring and adjustments are essential for optimal outcomes.

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NONPHARMACOLOGICAL APPROACHES TO PAIN MANAGEMENT

Ablative procedures

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Summary: Peripheral Neurolysis and Surgical Approaches in Pain Management

1. Peripheral Neurolysis with Phenol:

  • Indications:

    • Patients with cancer prognosis less than a year or intractable, severe pain.

    • Used when temporary relief is achieved with nerve blockade.

  • Considerations:

    • Phenol injection induces permanent neurolysis.

    • Nonselective, affecting all nerve fibers.

    • Avoidance of limb and sacral segment nerve blockade to prevent sensory/motor impairments.

  • Complications:

    • Burning dysesthesia pain (anesthetic Dolorosa) may develop post-neurolysis.

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2. Sympathetic Blockade:

  • Causalgia Treatment:

    • Serial injections of local anesthetics for sympathetic blockade.

    • Effective for pain relief in causalgia.

    • Pain relief duration surpasses the agent's action.

  • Guidance Methods:

    • Fluoroscopy or CT guidance often necessary for accurate approach.

  • Specific Blocks:

    • Stellate Ganglion Block: for arm pain.

    • Celiac Plexus Blockade: for upper abdominal pain (e.g., pancreatic cancer).

    • Lumbar Sympathetic Blockade: for pelvic, rectal, and leg pain.

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3. Peripheral Surgical Approaches:

  • Nerve and Dorsal Root Transaction:

    • For well-localized or segmental pain syndrome.

    • Patients responsive to nerve block may benefit.

  • Sympathetic Ganglionectomy:

    • In causalgia patients responsive to sympathetic blockade.

    • Late occurrence of painful dysesthesias is common post-procedure.

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Conclusion: Peripheral neurolysis with phenol and sympathetic blockade, including specific blocks for targeted areas, are effective interventions for patients with severe, intractable pain. Surgical approaches like nerve transaction and sympathetic ganglionectomy are considered in well-localized pain syndromes. However, complications such as burning dysesthesias can occur post-procedure, emphasizing the need for careful patient selection and monitoring.

 

Summary: Central Surgical Approaches in Pain Management

  1. Anterolateral Spinal Cordotomy:

    • Procedure:

      • Transection of the lateral spinothalamic tract.

    • Indications:

      • Life expectancy of 12 months or less.

      • Failure of pharmacological interventions.

      • Effective for unilateral somatic, nociceptive pain in one leg or trunk.

    • Limitations:

      • Ineffectiveness for visceral and neuropathic pain syndromes.

      • Development of painful dysesthesias over time.

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  1. Bilateral Thoracic Cordotomies:

    • Indications:

      • Midline lower abdominal, pelvic, or bilateral leg pain.

    • Results:

      • Initial pain control in about 80%.

      • Pain recurrence in 50% within 6-12 months.

      • 20% develop painful dysesthesias in a year.

    • Limitations:

      • Risk of urinary and fecal incontinence.

      • Potential corticospinal tract deficits.

      • Rarely, respiratory failure in patients on high narcotic doses.

​​

  1. Other Ablative Targets:

    • Locations:

      • Periaqueductal gray, trigeminal nucleus, thalamus, primary sensory cortex, frontal lobes, cingulate gyrus.

    • Comparison:

      • No procedure superior to cordotomy for pain originating below the cervical level.

      • Lesion of the cingulate gyrus interferes with emotional experience without producing analgesia.

  2. Pituitary Ablation:

    • Procedure:

      • Alcohol installation via transsphenoidal approach.

    • Indications:

      • Pain from disseminated bone metastasis in hormonally sensitive cancers (e.g., breast, prostate carcinoma).

 

Summary: Modulation Procedures in Pain Management

  1. Gate Theory and TENS (Transcutaneous Electrical Nerve Stimulation):

    • Concept:

      • Peripheral stimulation reduces nociceptive input (gate theory).

    • Procedure:

      • TENS is commonly used in clinical practice.

      • Placebo effect significantly contributes to its analgesic efficacy.

  2. Dorsal Root Fibers and Dorsal Column Stimulation:

    • Indications:

      • Poor efficacy of standard medical therapy.

      • Neuropathic pain syndrome without a primary central cause.

      • Dermatomal distribution of pain.

    • Procedure:

      • Electrodes inserted in dorsal epidural space via laminectomy or percutaneously.

      • Permanent implantation after a 4-7 day trial if there's pain relief.

    • Common Applications:

      • Chronic lumbosacral pain (failed back syndrome, arachnoiditis).

      • Neuropathy.

    • Results:

      • 50-70% show initial improvement.

      • Long-term relief in 40%, but some may still require analgesic medications.

  3. Stimulation of PAG and Primary Nuclei for Neuropathic Pain:

    • Indications:

      • Neuropathic pain syndrome with deafferentation components.

    • Procedure:

      • Stimulation of periaqueductal gray (PAG) and primary nuclei of spinothalamic and trigeminothalamic pathways.

    • Applications:

      • Postherpetic neuralgia in the face.

      • Central pain after cerebral infarction.

      • Post-cordotomy pain.

      • Pain after brachial plexus avulsions.

    • Results:

      • 50% of those with a good initial response report long-term benefits.

  4. Other Stimulation Areas:

    • Motor cortex and septal area stimulation used in pain control.

 

Summary: Neuronal Circuits and Pain Management

Neuropathic Pain:

  • Definition: Pain arising from neural pathway pathology (nerves, spinal cord, and brain).

  • Common Causes: Neuropathy, diabetes, chronic alcoholism, autoimmune disorders.

  • Treatment Approaches:

    • Nonmedical:

      • Devices.

    • Medications:

      • NSAIDs, triptans.

      • Injections (Botox, CGRP receptor blockers).

    • Exercise:

      • Varied activities (weights, running, yoga, martial arts, sports).

    • Soft Tissue Pain Management:

      • Custom shoes, shoulder restraints, assistive devices.

    • Sleep:

      • Importance of adequate, quality sleep.

      • NREM and REM sleep cycles.

      • Disorders like sleepwalking, sleep talking, nightmares, night terrors, REM sleep behavior disorder, sleep paralysis.

    • Diet:

      • Emphasis on anti-inflammatory diets.

      • Avoidance of inflammatory carbohydrates.

      • Inclusion of balanced and saturated fats.

Conclusion:

  • Pain Treatment Approach:

    • Rooted in understanding the mechanisms of pain generation.

    • Complex neurophysiological processes involved.

    • Pain can arise from normal responses to tissue injury, pathological alterations in neural activity, or without identifiable pathology.

  • Therapeutic Success:

    • Higher likelihood in nociceptive pain compared to neuropathic and idiopathic pain syndromes.

  • Importance of Understanding Mechanism:

    • Essential for formulating rational therapeutic strategies.

  • Treatment Goal:

    • Complete pain relief, often not aggressively pursued.

  • Disease Activity Indicator:

    • Progressive pain is a moderately sensitive and specific indicator for neoplastic, infectious, and inflammatory diseases.

  • Analgesic Toxicity:

    • Significant factor limiting complete relief of nociceptive and neuropathic pain.

​

Neuronal circuits that modulate pain

​

Summary: Gate Control Theory and Analgesia Systems

Gate Control Theory:

  • Proposed by: Melzack and Wall in the mid-1960s.

  • Concept: Non-painful input closes gates to painful input to the Central Nervous System (CNS).

  • Mechanism:

    • Collaterals of large sensory fibers activate inhibitory interneurons.

    • Inhibitory interneurons modulate pain transmission information carried by pain fibers.

  • Prediction:

    • Non-noxious stimulation at the spinal cord level produces presynaptic inhibition on dorsal root nociceptor fibers, blocking incoming noxious information.

  • Application:

    • Transcutaneous Electrical Nerve Stimulation (TENS) leverages this method for pain management.

​​

Stimulation Produced Analgesia (SPA):

  • Evidence: Demonstrated by intracranial electrical stimulation of specific brain sites (periaqueductal gray, nucleus raphe magnus, dorsal raphe, caudate nucleus, septal nucleus, etc.).

  • Effect:

    • Inhibits pain without behavioral suppression.

    • Touch, pressure, and temperature sensations remain intact.

​​

Stress-Induced Analgesia (SIA):

  • Definition: Analgesic reaction in response to painful or stressful events.

  • Insight into Endogenous Pain Control:

    • Provides insight into psychological and physiological factors activating endogenous pain control and opiate systems.

  • Observations:

    • Soldiers, athletes report not feeling pain during battle or game but experience it later.

    • Endogenous opiates released in response to stress may inhibit pain by activating the midbrain descending system.

  • Cross-Tolerance:

    • Some SIA exhibits cross-tolerance with opiate analgesia, indicating mediation via opiate receptors.

  • Variants:

    • Both opiate and non-opiate forms of SIA observed experimentally.

CONTACT INFORMATION

604 841 3398
gurwantg@gmail.com

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