Does the tibial and sural nerve transection model represent sympathetically independent pain?

Abstract

Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.

Fig. 1

Behavioral tests were performed before (0) and 2, 4, and 6 days after tibial and sural nerve transection (TST2, TST4, and TST6, respectively). On the 7th day after nerve transection, a sympathectomy or sham operation was performed. Behavioral tests were repeated at 1, 3, 7, and 14 days after sympathectomy (SYM1, SYM3, SYM7, and SYM14, respectively). (A) Paw withdrawal thresholds to von Frey stimulation. All values of tactile threshold after TST4 were significantly decreased compared to that before injury (p < 0.05), and there were no differences of threshold between sympathectomy and sham group at any time point. (B) Incidence of paw withdrawals to acetone application. All values of response frequency to acetone after TST2 were significantly increased compared to that before injury (p < 0.05), and there were no differences in response frequency between sympathectomy and sham group at any time point. Surgical sympathectomy altered neither the withdrawal thresholds to von Frey stimulation nor the frequency of paw withdrawal to acetone application compared to those on TST6.

Fig. 2

Temperature of the plantar skin of the hind paw before and after sympathectomy. The skin temperatures of both sides were significantly increased after sympathectomy compared to those measured before sympathectomy respectively (p < 0.05).

Fig. 3

Comparison of infra red thermography before (A) and after (B) sympathectomy. The differences of temperature between the trunk (○) and the ipsilateral (▿) or contralateral (□) hind paw were defined as ΔT1 or ΔT2, respectively. Both ΔT1 and ΔT2 were significantly decreased after sympathectomy compared to those taken before the sympathectomy respectively (p < 0.05).