Chronic pain represents a major public health challenge. Neuropathic pain, resulting from damage to the somatosensory system, is especially difficult to manage. Integrative treatments, such as acupuncture and bee venom acupuncture, are emerging as alternative options. This study aimed to assess the analgesic effects of apitoxin, injected at the Zusanli acupoint (ST36), for neuropathic pain management, and to explore whether melittin, a key component of apitoxin, could also provide analgesia. Additionally, it was explored whether both toxins could also prevent the onset of chronic pain. Male and female Wistar rats underwent sciatic nerve constriction to induce neuropathy. Apitoxin or melittin treatments were administered on days 1 or 15 post-surgery. Pain thresholds were measured before and after treatment, and spinal cord (SC) or dorsal root ganglion (DRG) tissues were collected for analysis of neuroinflammation markers (IBA-1, GFAP, ERG) on days 19 or 20. Naloxone was administered for opioid signaling evaluation. Results showed that both apitoxin and melittin significantly increased nociceptive thresholds, indicating analgesic effects in mechanical and thermal tests. This effect was longer-lasting than manual acupuncture and reversed by naloxone. Both toxins were able to delay the onset of chronic pain when early administered. Western blot analyses confirmed a reduction in neuroinflammation markers in both SC and DRG tissues. Furthermore, pharmacoacupuncture promoted analgesia in female rats, though the effects were not as long-lasting as in males. This study supports the potential of pharmacoacupuncture with apitoxin or melittin as an effective therapy for managing and delaying the onset of neuropathic pain.

This article presents pharmacoacupuncture with apitoxin or melittin as a potential approach for the relief and prevention of chronic pain. This technique may support clinicians in the management of pain and the restoration of clinical parameters, thereby contributing to patient care.