. Author manuscript; available in PMC: 2013 May 9.

Published in final edited form as: Hematology Am Soc Hematol Educ Program. 2010;2010:403–408. doi: 10.1182/asheducation-2010.1.403

Table 1.

Neural Mechanisms of Pain: Facilitating and Inhibiting Factors

Anatomical Structure	Neurotransmitters, Neurochemicals or Receptors	Modulatory Effect on Transduction or Transmission (F: Facilitation; I: Inhibition	Examples of modulating Drugs (Inhibit facilitation or enhance inhibition of pain transduction or transmission)

Peripheral Nervous System PAN Terminal	Leukotriene Prostaglandins Potassium Histamine Bradykinin Serotonin Substance P Endorphin	Transduction F, sensitizes F, sensitizes F, sensitizes F, sensitizes F, sensitizes F, sensitizes F, sensitizes I	corticosteroids, ketoprofen NSAIDs, e.g., ASA n/a antihistamines n/a n/a n/a opioids
Fiber	Na+, K+exchange across the cellular membrane	F, Transmission of action potential to CNS	mexiletine, tocainide, EMLA

Autonomic Nervous System	Norepinephrine	Transduction F, sensitizes nociceptive state F, activates neuropathic state	anxiolytics

Spinal Cord	Substance P, glutamate, and others serotonin (5HT_1B and 5HT₃) norepinephrine mu delta kappa GABA_A GABA_B	F, Transmission to projection cell (2^nd order neuron) F, Transmission with wind-up	opioids ketamine dextromethorphan TCAs TCAs, clonidine opioid agonists (e.g. morphine) opioid agonists opioid antagonist-agonists benzodiazepines baclofen

Brain	Substance P, glutamate, and others	F, Transmission to 3^rd or 4^th order neuron	opioids

Key: PAN=primary afferent nociceptor; ASA=aspirin; NSAIDs=nonsteroidal antiinflammatory drugs; n/a=not available or not applicable; Na+=sodium; K+=potassium; CNS=central nervous system; TCAs=tricyclic antidepressant drugs or other re-uptake inhibitor drugs. © 2001 D.J. Wilkie, used with permission.