# Reserpine-induced fibromyalgia model in female rats is a long-lasting painful condition masked by antinociceptive endogenous opioids

## TL;DR

Reserpine causes long-term pain in female rats, which is hidden by the body's own pain-relieving opioids.

## Contribution

The study reveals that reserpine-induced pain is masked by endogenous opioids and spinal opioid receptor activation.

## Key findings

- Reserpine-induced pain resolves by day 21 but is masked by opioid effects.
- Blocking opioids reinstates hypersensitivity, showing opioid involvement in pain suppression.
- Reserpine increases serum β-endorphin concentration in female rats.

## Abstract

Fibromyalgia (FM) is a chronic painful condition that primarily affects women. The allodynia and hyperalgesia induced by reserpine is a FM model commonly used to study the disease; however, it produces one painful episode, in contrast to FM, which is a chronic painful condition. Reserpine induces hypersensitivity for 10 days, which is resolved by day-21. In this study, we sought to determine whether the resolution of pain was due to the release of endogenous antinociceptive opioids and the activation of spinal opioid receptors.

Female Wistar rats were used in this study. To induce a fibromyalgia-like model, reserpine was subcutaneously administered. Twenty-one days after reserpine administration, subcutaneous or intrathecal opioid blockers were administered to evaluate latent sensitization. Additionally, serum β-endorphin concentration was determined by ELISA.

Reserpine produced transitory hyperalgesia and allodynia, which was resolved by day 21. Systemic administration of naloxone on days 21, 33, and 45 reinstated hypersensitivity. Likewise, intrathecal administration of naltrexone or specific antagonists of μ and δ opioid receptors (CTOP and naltrindole) reinstated hypersensitivity. These results suggest that an increased concentration of opioid agonists in reserpinized animals leads to antinociceptive effects. Accordingly, reserpine injection enhanced serum β-endorphin concentration in female rats.

Our data suggest that reserpine-induced nociceptive hypersensitivity is a long-lasting condition masked by the compensatory release of β-endorphin and the activation of spinal µ and, to a lesser extent, δ opioid receptors.