Vasodilatation in hyperalgesic rat skin evoked by stimulation of afferent A beta-fibers: further evidence for a role of dorsal root reflexes in allodynia.
In areas of secondary hyperalgesia, innocuous mechanical stimuli evoke pain (allodynia). We have proposed that this is produced by a central pre-synaptic interaction whereby A beta-fibers evoke spike activity (dorsal root reflexes) in nociceptive afferents (Pain, 68 (1996) 13). This activity should conduct centrally, evoking allodynia, and peripherally, evoking neurogenic vasodilatation. Here we tested this hypothesis by examining the effects of electrical stimulation of A beta-fibers on cutaneous blood flow before and after producing secondary hyperalgesia in anesthetized rats. Cutaneous blood flow was recorded in the hind paw skin innervated by the sural nerve using a laser Doppler flowmeter. The sural nerve was prepared for electrical stimulation, and the evoked activity was recorded from the sciatic nerve in continuity. Electrical stimulation (1 Hz, 4 x 0.2 ms pulses, 20 s) was applied to the sural nerve at 2T (A beta-fibers only) and 4T and 6T (A beta + A delta-fibers). Flux was recorded at baseline and after capsaicin or mustard oil application outside the sural nerve territory. The effects of intravenous administration of the calcitonin gene-related peptide (CGRP) receptor antagonist, alpha-CGRP(8-37), or of section of the sciatic nerve or of the L4-L6 dorsal roots were examined. Selective activation of the sural nerve A beta-fibers reliably evoked increases in cutaneous blood flow close to areas of chemical irritation or skin damage. A beta-fiber-evoked vasodilatation was abolished by sciatic nerve or dorsal root section and had a spatial arrangement and optimal stimulation pattern suggesting a central synaptic interaction similar to that responsible for dorsal root reflexes. The flux increases were dose-dependently and reversibly inhibited by alpha-CGRP(8-37), indicating that the A beta-fiber-evoked vasodilatation resulted from the antidromic activation of nociceptive cutaneous afferent fibers. These results support our hypothesis by showing activation of nociceptive primary afferents by A beta-fibers in areas of allodynia in a manner consistent with a pre-synaptic interaction evoking dorsal root reflexes.
Garcia-Nicas
E
E
Department of Physiology, University of Alcalá, Alcalá de Henares, E-28871 Madrid, Spain Research Unit, 'Principe de Asturias' University Hospital, Alcalá de Henares, E-28880 Madrid, Spain.
Laird
J M A
JMA
Cervero
F
F
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin; D004558:Electric Stimulation; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008916:Miotics / Q000494:pharmacology; D009149:Mustard Plant; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010936:Plant Extracts; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D019051:Rhizotomy; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D013126:Spinal Nerve Roots / Q000166:cytology / Q000502:physiology*; D013497:Sural Nerve / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008916:Miotics; D010446:Peptide Fragments; D010936:Plant Extracts; D010938:Plant Oils; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; C027793:mustard oil