The Antiallodynic Effect and the Change of the alpha2 Adrenergic Receptor Subtype mRNA Expression by Morphine Administration in a Spinal Nerve Ligation Rat Model

Chung, Kyu Yeon; Shin, Sang Wook; Kwon, Su Ah; Kim, Tae Kyun; Baek, Seung Hoon; Baik, Seong Wan

Abstract

BACKGROUND: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the alpha2 adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes.
METHODS
We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the alpha2 subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR).
RESULTS
Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the alpha2A, alpha2B, alpha2C subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results.
CONCLUSIONS
Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of alpha2 receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the alpha2 subtype gene expression.