What is Pain? Nociception “defines the processing of information about damaging stimuli by the nervous system to the point where perception occurs at the cerebral cortex and other subcortical structures” If a damaging stimulus is not perceived, is it pain?

Nociceptors A. Conduct information about noxious events to the dorsal horns 1. have higher activation threshold than most receptors 2. somatic: skin, muscles, joints 3. visceral: thoracic and abdominal cavities stretch, chemicals, ischemia

B. Will usually synapse on spinal interneurons

C. Two types of nociceptors 1. high-threshold mechanoreceptor (HTM) a. activated by intense mechanical stimulation b. innervated by thinly myelinated A-delta fibers - conduct at 5-30 m/sec - sharply localized pain

C. Two types of nociceptors 2. polymodal nociceptors (PMN) a. activated by intense mechanical stimulation, temperatures above 42˚C, and irritant chemicals b. innervated by unmyelinated C fibers - conduct at m/sec - poorly localized pain (dull)

Pain Mediators and Transmitters A. Can activate or sensitize nociceptors 1. ATP 2. bradykinin 3. histamine 4. prostaglandins B. Substance P 1. can be released peripherally at the damage site 2. can trigger primary hyperalgesia - usually short duration

Types of Pain A. Secondary hyperalgesia 1. light touch outside immediate area of cutaneous damage causes pain 2. not necessarily associated with receptor sensitization B. Allodynia 1. light touch on skin can cause severe pain 2. may involve release of substance P in dorsal horns - increases receptive field sizes and sensitivity - chronic nature may be enhanced by glutamate on NMDA receptors

C. Complex regional pain syndrome (CRPS) 1. reflex sympathetic dystrophy (RSD) is one type 2. RSD is an incompletely understood response of the body to an external stimulus, resulting in pain that usually is non-anatomical and disproportionate to the inciting event or expected healing response Types of Pain

C. Complex regional pain syndrome (CRPS) 3. is clinically defined as an “excessive or exaggerated response to an injury of an extremity, manifested by four somewhat constant characteristics”* a. intense or unduly prolonged pain b. vasomotor disturbances c. delayed functional recovery d. various associated trophic changes * Schutzer SF, Gossling HR. The treatment of reflex sympathetic dystrophy syndrome. J Bone Joint Surg Am. Apr 1984;66(4): nociceptive nerve endings appear to start expressing adrenergic receptors Types of Pain

D. Phantom limb pain 1. caused by severing a peripheral nerve trunk a. generates ectopic foci for action potentials b. sensitive to both mechanical stimulation and SNS activity 2. triggers a neuroma at the stump Types of Pain

E. Referred pain 1. visceral nociceptive input carried on ANS fibers 2. synapse at their spinal level of origin Types of Pain - pain in superficial regions in response to internal damage

A. Mainly project into dorsal root - spinothalamics - spinoreticulothalamics Nociceptive Pathways 1. project up via tracts: - spinomesencephalics 2. cross at or just above level

- loss of pain and temperature sensation Nociceptive Pathways 3. will affected by syringomyelia syrinx

1. many contain endogenous opioids (enkephalins and endorphins) Nociceptive Pathways B. Descending projections 2. many opiate receptor types at these synapses ( , ,  )

1. spinothalamics (localization of pain) Nociceptive Pathways B. Ascending projections 2. spinoreticulothalamics (affective component of pain) - refers to the unpleasantness or emotional distress that invariably attends the sensation of physical pain

1. primary sensory cortex (SmI) Nociceptive Pathways C. Cortical projections 2. secondary sensory cortex (SmII) 3. lesions alter perception but do not necessarily produce analgesia

4. also some projections to hypothalamus Nociceptive Pathways C. Cortical projections

1. aspirin, paracetamol, ibuprofen, naproxen Pain Management A. NSAIDs 2. inhibit cyclo-oxygenase (COX) - enzyme in production of prostaglandins - PGs potentiate effects of other pain mediators 3. COX-2 inhibitors - potential GI side effects valdecoxib (Bextra), celecoxib (Celebrex)

1. based on the gate theory Pain Management B. TENS (transcutaneous nerve stimulation) 2. may also trigger endorphin release

1. active ingredient in red chilis Pain Management C. Capsaicin 2. initially triggers release of substance P 3. can topically treat postherpetic neuralgia

1. good for relieving visceral pain Pain Management D. Opioids - NSAIDS not so good 2. morphine 3. heroin (dimorphine) more lipid soluble than morphine more rapid onset of activation when injected 4. fentanyl (IV or transdermal) 5. methadone - long duration/less sedation (no buzz) 6. buprenorphine (Temgesic, Buprenex, Suboxone, Subutex) 7. tramadol (Ultram and Ultram® ER) 8. codeine (methylmorphine) analgesic, antitussive and antidiarrheal

Pain Management D. Opioids 9. dextropropoxyphene (Darvocet-N and Darvon) 10. oxycodone (OxyContin, Percocet, Percodan) 11. hydrocodone (dihydrocodone) - Vicodin, Symtan, Anexsia, Dicodid, Hycodan, Hycomine, Hycet, Lorcet, Lortab, Norco, Novahistex, Hydrovo, Duodin, Kolikodol, Orthoxycol, Mercodinone, Synkonin, Norgan, and Hydrokon - intermediate-strength analgesic and antitussive - good for those allergic to codeine - stronger than codeine, but about half as potent as morphine

Pain Management D. Opioids 12. naloxone (Narcan) opioid receptor antagonist reverses effects of opioids (acute OD treatment) 13. naltrexone (Revia and Depade) opioid receptor antagonist long-term dependence control (actually better for alcoholism)

Pain Management E. Ondansetron (Zofran) 1. relieves opioid withdrawal symptoms without side effects 2. serotonin 5-HT 3 receptor antagonist 3. primary use is for preventing nausea (chemo, pregnancy)