Sarpogrelate Hydrochloride, a 5-HT2A Receptor Antagonist, Attenuates Neurogenic Pain Induced by Nucleus Pulposus in Rats

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Abstract

Study Design.

An in vivo study using a rat lumbar disc herniation model.

Objectives.

To evaluate the effects of sarpogrelate hydrochloride on neurogenic pain induced by nucleus pulposus translocation and to elucidate its mechanism.

Summary of Background Data.

Sarpogrelate, an antiplatelet agent with selective 5-hydroxytryptamine (5-HT) receptor 2A antagonist activity, has been reported to improve low back pain, sciatica, and numbness of lower extremities in patients with lumbar disc herniation. However, the efficacy of sarpogrelate for pain relief in this situation has not been established by clinical studies and its mechanism remains unknown.

Methods.

The autologous nucleus pulposus was placed onto the left L4 and L5 nerve roots of 30 Sprague-Dawley rats allotted to sarpogrelate (100 mg/kg, n = 15) and control (vehicle, n = 15) treatment groups. Sarpogrelate or vehicle was administered orally once daily between days 7 and 14 after surgery. Mechanical allodynia was measured before and after treatment. The right and left nerve roots and dorsal root ganglions were isolated from 5 animals in each group to assay 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine on day 5 of administration (= day 11 after surgery).

Results.

Sarpogrelate treatment significantly reduced mechanical allodynia on days 5 and 8 of administration. The placement of the nucleus pulposus onto nerve roots increased norepinephrine but not 5-HT and 5-HIAA contents in inflamed nerve roots or dorsal root ganglions. Sarpogrelate did not affect these levels.

Conclusions.

Sarpogrelate attenuated pain-related behavior induced by the nucleus pulposus in the animal model. Although further investigation is needed concerning the mechanism of action, this study supported the hypothesis that sarpogrelate is efficacious for treating the pain of lumbar disc herniation.

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