Behavioral manifestations of neuropathic pain and mechanical allodynia, and changes in spinal dorsal horn neurons, following L4-L6 dorsal root constriction in rats

We investigated behavioral symptoms of neuropathic pain, and associated cha nges in dorsal horn neurons, in a rat model involving loose ligation of lum bar dorsal roots. The L4-L6 dorsal roots were exposed unilaterally and loos ely constricted central to the respective ganglia with one (1-ligation) or two (2-ligation) silk 7-0 ligatures. In control groups the dorsal roots wer e exposed but not ligated (sham-operated), or sutures were placed lengthwis e between the dorsal roots (suture control). There was a significant reduct ion in mechanical withdrawal threshold on the operated side in both 1- and 2-ligation groups which began at 3 days, peaked at 2-5 week, and gradually recovered. A delayed threshold reduction was also seen on the non-operated side. Immediately post-surgery there was a significant increase (hypoalgesi a) in thermal paw withdrawal latency (Hargreaves test) in 1- and 2-ligation groups on the operated (but not non-operated) side that recovered after 1 week. Significantly less weight was borne by the operated limb 1-5 weeks po st-operatively in 1- and 2-ligation groups. The force of hind Limb withdraw als elicited by graded noxious heat pulses (38-52 degrees C) was significan tly lower 1 week post-surgery on the operated side (I-ligation group) follo wed by recovery. Withdrawal forces were higher 5-9 week post-surgery on the non-operated side in 1- and 2-ligation groups. We found no evidence of col d allodynia. Neither sham-operated nor suture controls showed any signs of allodynia or hyperalgesia. Following behavioral testing, rats were anesthet ized with halothane for single-unit recordings from lumbar wide dynamic ran ge-type (WDR) neurons. At 22 week post-surgery, the mean area of mechanosen sitive receptive fields was significantly larger for units on the operated side in 1- and 2-ligation groups compared with those on the non-operated si de or with those from sham-operated rats. Mean stimulus-response functions to graded noxious heat pulses (38-52 degrees C, 5 s) were not significantly different between operated and nonoperated sides for 1- or 2-ligation grou ps, or compared with the 22-week sham-operated group. At 5 week post-surger y, the mean area of cutaneous receptive fields, and stimulus-response funct ions to graded noxious heat, were not significantly different between units recorded on operated versus non-operated sides, or compared with units fro m 5-week sham-operated rats. Spontaneous unit activity was significantly hi gher on the operated versus non-operated side in the 2-ligation (22-week) a nd sham (5-week) groups. Enlarged cutaneous receptive fields of dorsal horn neurons may contribute to mechanical allodynia associated with dorsal root constriction. However, the slow (>5 week) development of receptive field e nlargement does not match the rapid development of allodynia. The lack of e ffect of dorsal root constriction on thermal sensitivity of dorsal horn uni ts ipsilaterally corresponds to the lack of marked thermal hyperalgesia obs erved behaviorally. (C) 1999 International Association for the Study of Pai n. Published by Elsevier Science B.V.