Possible impact of genetic differences on the development of neuropathic pain-like behaviors after unilateral sciatic nerve ischemic injury in rats

The development of neuropathic-like behaviors following unilateral ischemic injury to the sciatic nerve was examined and compared in four rat strains: Sprague-Dawley (SD), Wistar-Kyoto (WK), spontaneously hypertensive (SHR) a nd Dark-Agouti (DA). We have also compared two sub-strains of SD rats suppl ied from two different vendors (SD-BK and SD-DK). The responses to mechanic al, heat or cold stimuli of both hind paws were measured before and regular ly after injury for up to 10 weeks. Spontaneous paw lifting and changes in paw posture after nerve injury were also examined. Significant differences in basal sensitivity to mechanical or heat stimulation were seen among the four rat strain studied with SHR and DA rats being less sensitive than the SD and WK rats. All strains of rats developed bilateral mechanical allodyni a and ipsilateral heat hyperalgesia after photochemically-induced nerve isc hemia, but the time-course and magnitude of the responses were significantl y different among the strains. Again, the SHR and DA were found to be least susceptible to the development of abnormal pain-like responses. Cold allod ynia occurred only in WK and SD-BK. SD-DK rats on the other hand developed more severe mechanical allodynia than SD-BK. SHR and DA rats showed less de ficits in paw posture after nerve injury whereas spontaneous pain lifting, a measure of possible spontaneous pain, was comparable among all strains. L ight microscopic study of the injured sciatic nerve showed comparable nerve damage in SHR, WK and two sub-strains of SD rats. The DA rats however exhi bited reduced area of intraneural damage. Finally, electronmicroscopic exam ination revealed that damage to both myelinated and unmyelinated fibers occ urred in this model in all strains. These results showed that normal sensit ivity and the development of pain-like response after partial nerve injury differ substantially among different strains of rats, supporting the emergi ng concept that genetic factors affect pain sensitivity under normal condit ions and after nerve injury. The apparent resistance of DA rats to nerve is chemia, however, may suggest that genetic factors not directly related to p ain modulation also play a role in the diverse outcomes. Our results indica te that sub-strains of rats also showed variable development of neuropathic pain-like behaviors to both the modality and magnitude of the effect. Thus , controlling sub-strains is also important in experimental studies of neur opathic pain in rats. (C) 2001 International Association for the Study of P ain. Published by Elsevier Science B.V. All rights reserved.