Cesar J. Carranza-Aguilar
César J. Carranza-Aguilar, Ricardo Sanchez-Rojas, Silvia L. Cruz. Department of Pharmacobiology, Cinvestav, México.
Background: Fentanyl is an opioid that can cause withdrawal syndrome. Opioid withdrawal symptoms are similar for all opioids and include generalized pain, yawning, diarrhea, nausea, cramps, and memory loss. Since neuroinflammation contributes to opioid withdrawal, we studied if the glial inhibitor pentoxifylline could prevent hyperalgesia, somatic withdrawal signs, and short-term memory loss caused by cessation of repeated fentanyl administration.
Methods: Male Wistar rats (250-300 g) were intraperitoneally injected with fentanyl (0.1 mg/kg, 8 h apart, until reaching 7 administration) with or without pentoxifylline (20 mg/kg, -30 min). We used the tail-flick test to assess nociception, video recordings to evaluate somatic withdrawal signs and, the passive avoidance task test to measure short-term memory loss. Glial activation in the basolateral amygdala (BLA) was analyzed by detecting the ionized calcium-binding adapter protein (Iba1) in microglia and glial fibrillary acidic protein (GFAP) in astrocytes.
Results: Repeated fentanyl administration induced antinociceptive tolerance. Twenty-four hours after completion of treatment, fentanyl produced hyperalgesia, increased somatic signs of withdrawal (grooming, chewing, scratching, and wet-dog shakes), produced short-term memory loss, and increased microglía and astrocyte activation in the BLA. Pentoxifylline attenuated tolerance development and hyperalgesia, mitigated chewing and wet-dog shakes, protected against short-term memory loss, and inhibited glial activation in the BLA.
Conclusions: The anti-inflammatory drug pentoxifylline can prevent some effects during fentanyl withdrawal, such as hyperalgesia, short-term memory loss, and glial activation. Targeting neuroinflammation along opioid treatment could help to alleviate the negative experience of withdrawal.