PERI-ADMINISTRATION OF CLONIDINE OR MK801 DELAYS BUT DOES NOT PREVENTTHE DEVELOPMENT OF MECHANICAL HYPERALGESIA IN A MODEL OF MONONEUROPATHY IN THE RAT

Following loose ligation of the sciatic nerve, rats develop a persiste nt hyperalgesia which mimics some of the features of traumatic neuropa thy seen in man. Previously, we have shown that administration of MK80 1 or clonidine prior to and 30 min following loose ligation of the sci atic nerve prevented the development of hyperalgesia up to 30 days fol lowing surgery. In the current study, we have extended our observation s and examined the effect of administration of clonidine (1 mg/kg, s.c .) or MK801 (0.3 mg/kg, s.c.) 30 min prior to and 6 h following loose ligation of the sciatic nerve on the development of hyperalgesia asses sed at 9 time points between 16 and 150 days after loose ligation. We have found that compared with saline treatment, the degree of hyperalg esia apparent in animals receiving MK801 was significantly reduced whe n tested 16, 28 or 42 days after surgery. No significant difference be tween the 2 treatment groups was detected at any other time points dur ing the study. Similarly, when compared with saline treated controls, the degree of hyperalgesia measured in animals following peri-administ ration of clonidine was significantly less when measured 16 and 28 day s after surgery, but did not differ significantly at any of the time p oints tested between 42 and 150 days following surgery. Our results in dicate that peri-administration of MK801 or clonidine significantly de lay, but do not prevent, the onset of neuropathic hyperalgesia.