Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion.
TRPV1 is expressed in a subpopulation of myelinated Aδ and unmyelinated C-fibers. TRPV1+ fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1+ Aδ-fibers. Here we show that stimulating either subtype of TRPV1+ fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1+ fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration Aδ stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same Aδ stimuli. The qualitative intensity of Aδ responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of Aδ responses with morphine suggest multiple roles for TRPV1+ Aδ fibers in nociceptive processes and their modulation of pathological pain conditions.
['Mitchell|Kendall|K|', 'Lebovitz|Evan E|EE|', 'Keller|Jason M|JM|', 'Mannes|Andrew J|AJ|', 'Nemenov|Michael I|MI|', 'Iadarola|Michael J|MJ|']
D000701:Analgesics, Opioid D000818:Animals D002351:Carrageenan D004195:Disease Models, Animal D004224:Diterpenes D004305:Dose-Response Relationship, Drug D006930:Hyperalgesia D007249:Inflammation D007834:Lasers D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009020:Morphine D009498:Neurotoxins D059225:Nociception D017288:Pain Threshold D010812:Physical Stimulation D051381:Rats D017207:Rats, Sprague-Dawley D050916:TRPV Cation Channels
Nociception Analgesia Capsaicin Chemoreceptors Chronic Pain