Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms

Abstract

1. Psychophysical studies were made, in humans, of the sensory characteristics and underlying mechanisms of the hyperalgesia (often termed "secondary hyperalgesia") that occurs in uninjured skin surrounding a local cutaneous injury. The hyperalgesia was characterized by lowered pain thresholds and enhanced magnitude of pain to normally painful stimuli. The "injury" was produced by a single intradermal injection of 10 microliters of 100 micrograms of capsaicin, the algesic substance in hot chili peppers. 2. On injection of capsaicin into the volar forearm, the subjects experienced intense burning pain, accompanied immediately by the formation of three areas of hyperalgesia surrounding the injection site. The largest mean area (55 cm2) was hyperalgesic to a normally painful punctate stimulation of the skin. Nested within this was an area of tenderness to gentle stroking (38 cm2) and a much smaller area of hyperalgesia to heat (2 cm2). An area of analgesia to pinprick, approximately 4 mm in diameter and centered on the injection site, developed within minutes and typically disappeared within 24 h. The hyperalgesia to heat and to stroking disappeared within 1-2 h, whereas the hyperalgesia to punctate stimuli, although gradually decreasing in area, lasted from 13 to 24 h. 3. The radial spread of the mechanical hyperalgesia (to punctate and stroking stimuli) away from the injury was dependent on neural activity and not produced, for example, by algesic substances transported away from the injury. The injection of capsaicin into a small area of anesthetized skin did not produce hyperalgesia in the surrounding, unanesthetized skin. Also, the hyperalgesia in normal skin readily crossed a tight arm band that blocked the circulation of blood and lymph. 4. The spread of mechanical hyperalgesia away from the injury was peripherally mediated via cutaneous nerve fibers because it was blocked by a thin mediolateral strip of cutaneous anesthesia placed 1 cm away from the capsaicin injection site. Hyperalgesia developed normally on the capsaicin side of the strip but not on the other side. 5. Heat stimulation of the skin that produced pain that was equivalent in magnitude and time course to that produced by an injection of capsaicin (10 micrograms) resulted in much smaller areas of mechanical hyperalgesia. It was postulated that there exist special chemosensitive primary afferent nerve fibers that are more effective in producing mechanical hyperalgesia than are the known thermo- and mechanosensitive nociceptive nerve fibers. 6. Once developed, the mechanical hyperalgesia became only partially dependent on peripheral neural activity originating at the site of injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

“…Hyperalgesia is induced following injury or inflammation, but can also be produced after skin application of substances that activate or sensitize nociceptors. A classic example of algogen induced heat and mechanical hyperalgesia is that following application of capsaicin to the skin (LaMotte et al, 1991). While working on the role of NGF in determining the phenotypic identity of nociceptors in Lorne Mendell's lab (Ritter et al, 1991;Lewin et al, 1992a), Amy Ritter and Gary Lewin noted that rats that had been exposed to daily injections of NGF were behaviorally more sensitive to mechanical and heat stimuli than untreated animals.…”

Prevalence of somatic small fiber neuropathy in obesity

“…In skin, these capsaicin-sensitive nociceptive afferents play a significant role in sensory function, particularly a nocifensor role 17 in tissue protection due to their ability to: (1) convey pain signals to the CNS upon stimulation by noxious mechanical, thermal and irritant chemical stimuli; (2) elicit a pruritic reaction; 26 (3) cause sensitization of the skin (e.g., to heat) decreasing the pain threshold, a process defined as primary hyperalgesia 22,[27][28][29][30] (4) evoke an axon-reflex flare or neurogenic vasodilatation. 21,31,32 All four of these reactions, acute heat pain, pruritis, sensitization and flare reactions, are C-fiber mediated, apparently by utilizing different sub-sets of C-fibers.…”

Modulation of I A Currents by Capsaicin in Rat Trigeminal Ganglion Neurons

“…The initial painful sensation after capsaicin application arises from the selective activation of vanilloid receptors in capsaicin-sensitive nociceptors that leads to depolarization and the generation of action potentials (APs) (Baumann et al 1991;Gold et al 1996a;Heyman and Rang 1985;LaMotte et al 1991;Williams and Zieglganberger 1982). Our goal is to investigate mechanisms by which capsaicin can initiate hyperalgesia in rat trigeminal ganglion (TG) neurons.…”