Comparing Partial and Total Tibial-Nerve Axotomy: Long-Term Effects on Prevalence and Location of Evoked Pain Behaviors

Monophasic (one-time) nerve injuries heal without clinically significant residua in most cases, but rare individuals are left with neuropathic pain, even after seemingly minor lesions. The effects of lesion size on risk for chronic pain persistence are not well understood, particularly as concerns the complex regional pain syndrome, which is defined in part by pain "disproportionate" to the severity of the causative lesion, and extending outside the autonomous territory of a single nerve. To better clarify the expected prevalence of pain behaviors after nerve injury, we compared the effects in rats of different-sized axotomies on the prevalence and location of evoked pain behaviors. To highlight clinical relevance, we also describe a patient with iatrogenic tibial-nerve injury causing similar chronic neuralgia. Adult male Sprague-Dawley rats were anesthetized and had either 1/3, 2/3 or their entire left tibial nerves tightly ligated at two sites just below the sciatic trifurcation and the interposed nerve was cut. Unoperated rats provided controls. Sensory function in the tibial and sural-innervated territories of both plantar hindpaws was assessed for as long as 6 months postoperatively. Soon after surgery, evoked pain behavior developed in the ipsilesional sural-innervated site in a subset of axotomized rats and recovery was variable. The relationship between lesion size and prevalence and severity of hyperalgesia varied for different pain behaviors, with pinprick hyperalgesia clearly more likely after larger axotomies. In summary, partial tibial-nerve injury in rats models human disease and suggests that expectations of proportionality between lesion size and development of neuropathic pain may need revision.