Abstract

Bee venom (BV) has a long history of being used in traditional Korean medicine to relieve pain. Here, we investigated the effect of BV-derived phospholipase A2 (bvPLA2), a major component of BV, on peripheral nerve injury-induced neuropathic pain in rats. Spinal nerve ligation (SNL) was performed in Sprague Dawley rats to induce neuropathic pain, and paw withdrawal thresholds were measured using von Frey test. Mechanical allodynia, the representative symptom of neuropathic pain, was manifested following SNL and persisted for several weeks. The repetitive bvPLA2 treatment (0.2 mg/kg/day, i.p.) for two days significantly relieved the SNL-induced mechanical allodynia. The antiallodynic effect of bvPLA2 was blocked by spinal pretreatment with α1-adrenergic antagonist prazosin (30 μg, i.t.) but not with α2-adrenergic antagonist idazoxan (50 μg, i.t.). Also, the spinal application of α1-adrenergic agonist phenylephrine (50 μg, i.t.) reduced mechanical allodynia. These results indicate that bvPLA2 could relieve nerve injury-induced neuropathic mechanical allodynia through the activation of spinal α1-adrenergic receptors.

Highlights

  • Neuropathic pain is normally defined as pain caused by nerve damage or dysfunction of the somatosensory system and, unlike nociceptive pain, has no warning function useful for survival.Neuropathic pain patients experience symptoms of allodynia, hyperalgesia, and painful sensation like shooting, burning, and tingling

  • -ARs.antagonist, could not block the analgesic effect of BV-derived phospholipase A2 (bvPLA2) (Figure 3d). These results indicate that the analgesic effects of bvPLA2 in Spinal nerve ligation (SNL)-induced mechanical allodynia are mediated by activation of spinal α1- but not α2ARs

  • We aimed to investigate whether bvPLA2 treatment could be a possible alternative treatment for nerve injury-induced neuropathic pain

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Summary

Introduction

Neuropathic pain is normally defined as pain caused by nerve damage or dysfunction of the somatosensory system and, unlike nociceptive pain, has no warning function useful for survival.Neuropathic pain patients experience symptoms of allodynia, hyperalgesia, and painful sensation like shooting, burning, and tingling. Anticonvulsants (e.g., gabapentin, pregabalin) and antidepressants (e.g., duloxetine) are currently being used for neuropathic pain patients. These treatments are only effective in a subset of patients, and there are adverse effects that restrict the use of the treatments for patients [1,2]. The analgesic effect of BV has been studied in various pain states, including formalin-induced pain, chemotherapy-induced peripheral neuropathy (CIPN), and nerve injury-induced neuropathic pain [4,5,6] These studies indicated the crucial role of noradrenergic system in analgesic effect of BV [5,6]

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