Peripheral nerve injury may lead to neuropathic pain that has been considered unresponsive to opioids. In animal models of neuropathic pain, there are previous data of both increased and decreased effect of opioids, but only limited information of the long-term effects of opioid treatment on the development of the symptoms of neuropathy. The possibility of preventing the development of signs of neuropathy with either a single pre-injury injection or chronic postinjury administration of morphine was studied in rats with unilateral peripheral neuropathy due to tight ligation of the L5 and L6 spinal nerves. These rats developed both mechanical and cold allodynia, but no thermal hyperalgesia. Neither subcutaneous morphine given as single injection (10 mg/kg) before the nerve injury nor chronic administration starting immediately after surgery using slow-release pellets (one, two or five pellets containing 75 mg of morphine, resulting in a total dose of 75, 150 or 375 mg) prevented the development of either mechanical or cold allodynia. No autotomy, signs of distress, altered social behaviour or morphine withdrawal was seen in any of the rats. The fact that neuropathic pain-like symptoms were not attenuated by any of the treatments studied could indicate that neither premedication nor postoperative pain management with systemic morphine is effective in preventing postoperative neuropathic pain. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.