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-definition of pain: an unpleasant sensory or emotional experience -perception of pain is a product of brains abstraction and elaboration of sensory input. -perception of pain varies with individuals and circumstances (soldier injured) -activation of nociceptors does not necessarily lead to experience of pain (asymbolia for pain; patient under morphine) -pain can be perceived without activation of nociceptors (phantom limb pain, thalamic pain syndrome) -important for survival, protect from damage: congenital and acquired insensitivity (diabetic neuropathy, neurosyphilis) to pain can lead to permanent damage -pain reflexes can be stopped if not appropriate (step on nail near precipice, burn hands while holding a baby. Pain can be suppressed if not needed for survival (soldier).
In general 2 clinical states of pain: Physiological (nociceptive) pain direct stimulation of nociceptors. Neuropathic (intractable) pain result from injury to the peripheral or central nervous system that causes permanent changes in circuit sensitivity and CNS connections.
CGRP
CGRP
A-beta
C fibers
Rheumatoid and Osteo-arthritis Back pain Menstrual Pain Labour Pain Peripheral Nerve Injuries Shingles Headache and Migraine Cancer Pain Trigeminal Neuralgia Phantom Limb Pain Sports Injuries Sciatica Aching Joints Post Operative Pain Muscular Pain Whiplash and Neck Injury and many others
Referred Pain:
Ascending Pathways:
->localization, intensity, type of pain stimulus
->arousal, emotion; involves limbic system, amygdala, insula, cingulate cortex, hypothalamus. Mediate descending control of pain (feedback loop)
New pathway for visceral pain: selective lesion of fibers in the ventral part of the fasciculus gracilis reduces dramatically the perception of pain from the viscera. General problems with surgery: Rhizotomy (cutting dorsal root) Anterolateral cordotomy (cutting ALS) In both cases, pain come back, excruciating. Thalamus: lesion VPL, VPM thalamic syndrome. Intralaminar nuclei (arousal + limbic) Cortex: S1 cortex localization, quality and intensity of pain stimuli. Lesion of cingulate gyrus and insular cortex asymbolia for pain
Multiple regression analysis (left panel) of positron emission tomography data revealed statistically reliable relationships between perceived pain intensity and activation of a functionally diverse group of brain regions, including those important in sensation, motor control, affect, and attention. Pain intensity-related activation occurred bilaterally in the cerebellum (CB), putamen, thalamus (Thal), insula, anterior cingulate cortex (ACC), and secondary somatosensory cortex (SII), contralaterally in the primary somatosensory cortex (SI) and supplementary motor area (SMA), and ipsilaterally in the frontal operculum (PMv).
Analgesics:
1) May act at the site of injury and decrease the pain associated with an inflammatory reaction (e.g. non-steroidal anti-inflammatory drugs (NSAID) such as: aspirin, ibuprofen, diclofenac). Believed to act through inhibition of cyclo-oxygenase (COX). COX-2 is induced at sites of inflammation. Inhibition of COX-1 causes the unwanted effects of NSAID, i.e. gastrointestinal bleeding and nephrotoxicity. Selective COX-2 inhibitor are now used. May alter nerve conduction (e.g. local anesthetics): block action potentials by blocking Na channels. Used for surface anesthesia, infiltration, spinal or epidural anesthesia. Used in combination to steroid to reduce local swelling (injection near nerve root). Local anesthetic preferentially blocks C fiber conduction, cold decreases firing of C fibers, ischemia blocks first the large myelinated fibers. May modify transmission in the dorsal horn (e.g. opioids: endorphin, enkephalin, dynorphin). Opioids act on G-protein coupled receptors: Mu, Delta and Kappa. Opioid agonists reduce neuronal excitability (by increasing potassium conductance) and inhibit neurotransmitter release (by decreasing presynaptic calcium influx)
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May affect the central component and the emotional aspects of pain (e.g. opioids, antidepressant). Problems of tolerance and dependence
Fusion molecule: i.e. use recombinant techniques to couple the extracellular domain of
trkA receptor to the Fc portion of human immunoblobin G, to produce a fusion protein that binds and neutralize the effects of NGF.