Contralateral Neuropathic Pain Following a Surgical Model of Unilateral Nerve Injury in Rats

Damage to peripheral nerves provokes chronic neuropathic pain that lasts beyond the duration of the nerve injury. The presence of pain signs have been reported in areas other than those attributed to the injured nerve, i.e., in contralateral regions. We evaluated the presence, magnitude, and chronology of mechanical and cold allodynia in the contralateral paw of rats undergoing unilateral ligation of the L5 and L6 spinal nerves. Twenty-three male Sprague-Dawley rats underwent spinal nerve ligation of the left L5 and L6 spinal nerves (SNL group) and 7 rats received a sham surgery without nerve ligation (sham group). Signs of mechanical allodynia as assessed with von Frey filaments, and cold allodynia as assessed with the acetone drop test, were studied before surgery and throughout 21 postoperative days. Responses of ipsilateral and contralateral paws of the SNL group were compared between themselves and with those in the sham group. Rats in the SNL group developed mechanical and cold allodynia responses in the ipsilateral paw, and also in the contralateral paw. Allodynia in the contralateral paw appeared later, becoming statistically significant on day 10 after surgery for mechanical allodynia and on day 21 for cold allodynia as compared with the sham group. Contralateral pain was of a lower intensity than on the ipsilateral side. After L5 and L6 spinal nerve ligation, rats developed mechanical and cold allodynia in the contralateral paw, suggesting extraterritorial development of neuropathic signs. This finding has implications for future study design and therapeutic approaches.