Time-course of spinal sensitization following carrageenan-induced inflammation in the young rat: a comparative electrophysiological and behavioural study in vitro and in vivo.
Inflammation of peripheral tissues evokes spontaneous pain and an increased responsiveness to external stimuli known as hyperalgesia, produced by both peripheral and central changes. The central component is initiated by a sustained afferent barrage produced by sensitized peripheral nociceptors, but it is unclear to which extent ongoing nociceptive input is required to maintain these central changes. Here, we have used an isolated preparation of the spinal cord in vitro obtained from eight- to 12-day-old rats to examine spinal plasticity in the absence of naturally occurring afferent inputs. Spinal reflex responses in preparations obtained from naive rats were compared with those from animals with carrageenan-induced inflammation of one hindpaw of 3 h, 6 h and 20 h duration prior to the extraction of the cord. Measurements of thermal (heat) and mechanical hyperalgesia in awake animals were also made at the same time-points. At 6 h post-carrageenan, there was a significant increase in the wind-up evoked by trains of high-intensity (C-fibre) stimuli, and at 20 h increased responses to both trains and single high-intensity stimuli, and a novel wind-up to low-intensity (Abeta-fibre) trains were observed. In contrast, maximal behavioural hyperalgesia was observed by 3 h post-carrageenan, and thermal hyperalgesia had resolved by 20 h, although mechanical hyperalgesia remained. These results show that the induction of spinal plasticity independent of peripheral input is a progressive process with a slow time-course, since significant hyperreflexia in the isolated spinal preparation appears 6 h after inflammation and develops further within 20 h. We conclude that during the first 3 h following inflammation, hyperalgesia is the result of peripheral sensitization and of central mechanisms that depend on an ongoing peripheral input and thus changes were not observed in the isolated spinal cord.
Department of Physiology, University of Alcalá, Madrid, Spain.
G
G
Hedo
J M
JM
Laird
J A
JA
Lopez-Garcia
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002351:Carrageenan; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D005260:Female; D006930:Hyperalgesia / Q000209:etiology; D066298:In Vitro Techniques; D008297:Male; D009187:Myelitis / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000503:physiopathology*; D013997:Time Factors
D002351:Carrageenan