Journal of Pain Research (Jan 2019)
Analgesic effects of calcitonin on radicular pain in male rats
Abstract
Yoshinori Terashima,1,2 Tsuneo Takebayashi,3 Shunsuke Jimbo,1 Izaya Ogon,1 Tatsuya Sato,2 Nobutoshi Ichise,2 Noritsugu Tohse,2 Toshihiko Yamashita1 1Department of Orthopaedic Surgery, School of Medicine, Sapporo Medical University, Sapporo 060-0061, Japan; 2Department of Cellular Physiology and Signal Transduction, School of Medicine, Sapporo Medical University, Sapporo 060-0061, Japan; 3Sapporo Maruyama Orthopaedic Hospital, Sapporo 060-0007, Japan Purpose: Radicular pain is a frequently observed symptom of lumbar disk herniation or lumbar spinal canal stenosis. Achieving radicular pain relief is difficult. This type of pain may progress to chronic neuropathic pain. Calcitonin (elcatonin [eCT]) has been used mainly for hypercalcemia and pain associated with osteoporosis. The purpose of this study was to investigate analgesic effects of repeated eCT administration on radicular pain in male rats and changes in mRNA-expression levels of voltage-dependent sodium channels in the dorsal root ganglion (DRG). Methods: Seventy male Sprague-Dawley rats were used. A right L5 hemilaminectomy and an L5–L6 partial facetectomy were performed to expose the right L5 nerve root. Under a microscope, the right L5 spinal nerve root was tightly ligated extradurally with 8-0 nylon suture proximally to the DRG to cause radicular pain in rats. Mechanical hyperalgesia, thermal hyperalgesia, and analgesic effects of eCT were compared among rats with radicular pain that received eCT, those that received the vehicle, and sham rats that received the vehicle. Real-time reverse-transcription PCR was performed to measure mRNA-expression levels of tetrodotoxin-sensitive (NaV1.3 and NaV1.6) and tetrodotoxin-resistant (NaV1.8 and NaV1.9) sodium channels in the DRG. Results: Mechanical and thermal hyperalgesic reactions occurring in rats with radicular pain significantly improved on days 5 and 9 of eCT administration, respectively. In rats with radicular pain, mRNA-expression levels of NaV1.3, NaV1.8, and NaV1.9 increased. After repeated eCT administration, mRNA-expression levels of these sodium channels in rats with radicular pain improved to the same levels as in sham rats. Conclusion: The present study demonstrated that repeated systemic eCT administration was effective for radicular pain. No serious side effects of eCT have been reported thus far. Therefore, calcitonin may be a preferred therapeutic option for patients with radicular pain or for those requiring long-term treatment. Keywords: radiculopathy, hyperalgesia, lumbar disk herniation, lumbar spinal canal stenosis, sodium channel, elcatonin