Peripheral mechanisms of pain and analgesia.
This review summarizes recent findings on peripheral mechanisms underlying the generation and inhibition of pain. The focus is on events occurring in peripheral injured tissues that lead to the sensitization and excitation of primary afferent neurons, and on the modulation of such mechanisms. Primary afferent neurons are of particular interest from a therapeutic perspective because they are the initial generator of noxious impulses traveling towards relay stations in the spinal cord and the brain. Thus, if one finds ways to inhibit the sensitization and/or excitation of peripheral sensory neurons, subsequent central events such as wind-up, sensitization and plasticity may be prevented. Most importantly, if agents are found that selectively modulate primary afferent function and do not cross the blood-brain-barrier, centrally mediated untoward side effects of conventional analgesics (e.g. opioids, anticonvulsants) may be avoided. This article begins with the peripheral actions of opioids, turns to a discussion of the effects of adrenergic co-adjuvants, and then moves on to a discussion of pro-inflammatory mechanisms focusing on TRP channels and nerve growth factor, their signaling pathways and arising therapeutic perspectives.
Stein
Christoph
C
Department of Anesthesiology and Critical Care Medicine, Charité Campus Benjamin Franklin, Freie Universität Berlin, Germany.
Clark
J David
JD
Oh
Uhtaek
U
Vasko
Michael R
MR
Wilcox
George L
GL
Overland
Aaron C
AC
Vanderah
Todd W
TW
Spencer
Robert H
RH
D000322:Adrenergic Agonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
D000322:Adrenergic Agonists; D000700:Analgesics; D000701:Analgesics, Opioid; D050051:Transient Receptor Potential Channels; D020932:Nerve Growth Factor