Epidural Sustained Release Ropivacaine Prolongs Anti-Allodynia and Anti-Hyperalgesia in Developing and Established Neuropathic Pain

Ropivacaine is a local anesthetic widely used for regional anesthesia and epidural analgesia, but its relatively short duration limits its clinical use. A novel sustained release lipid formulation of ropivacaine has been recently developed to prolong its duration. We examined the epidural anti-hypersensitivity and preemptive effects of ropivacaine in mesylate injection and sustained release suspension forms in a rat model of neuropathy produced by peripheral nerve injury. Epidural administration of ropivacaine mesylate injection specifically blocked mechanical allodynia and thermal hyperalgesia by approximately 50% with a biological half-effective duration of approximately 3 hrs. The equivalent dose of ropivacaine free-base in sustained release suspension significantly prolonged the duration of anti-allodynia and anti-hyperalgesia by approximately 2 times. Multiple daily epidural injections of ropivacaine in both the mesylate injection and sustained-release suspension forms did not induce tolerance or potentiation to anti-allodynia or anti-hyperalgesia. Moreover, the single or multiple daily administration of ropivacaine mesylate injection before surgery in particular, markedly blocked the initiation and development of neuropathic pain, increasing the biological half-effective duration from less than 4 hrs up to 1 or 2 days. The single and multiple daily epidural injection of ropivacaine sustained release suspension further delayed the biological half-lives to 2 and 3 days, respectively. Our results indicate that the epidural administration of ropivacaine effectively blocks neuropathic pain without the induction of analgesic tolerance, and significantly delays the development of neuropathy produced by peripheral nerve injury. Epidural ropivacaine sustained release suspension produces much longer blockade effects of mechanical allodynia and heat hyperalgesia, and more significantly delays the development of neuropathic pain.