Influence of intrathecal injection with dexmedetomidine on the behavioral ability and analgesic effects on rats with neuropathic pain and expression of protein kinase C in the spinal dorsal horn

Abstract

This study aimed to investigate the influence of intrathecal injection with dexmedetomidine on the behavioral ability and analgesic effects of rat models with chronic neuropathic pain. It also discusses the role that the expression of protein kinase C (PKC) in the spinal dorsal horn plays in the analgesic mechanism of dexmedetomidine. A total of 35 Sprague Dawley rats were selected. Five rats were randomly chosen as the blank control group and the rest were prepared as models with chronic constriction injury, which were divided into the model and the observation group (n=15, each group). The observation group was injected with 10 ml dexmedetomidine intrathecally, while the model group was injected with an equivalent amount of saline. The behavioral abilities were evaluated by cumulative and motor function score. In addition, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the detection of pain threshold. Immunohistochemistry staining method was used to test the positive expression of PKC, and western blot analysis was used for the detection of PKC quantitative expression levels. After initiation, the instant cumulative and motor function score of the model and observation groups increased, while the values of MWT and TWL decreased. After initiation, the positive expression of PKC in the spinal dorsal horn of the model and observation groups rose dramatically, and the quantitative expression level was also on the rise. The positive and quantitative expression levels in the observation group reduced gradually over time. Thus, the intrathecal injection of dexmedetomidine may improve the behavioral ability of rats with chronic neuralgia and reduce the degree of pain, which may be associated with the inhibition of the expression of PKC in the spinal dorsal horn.

Dexmedetomidine Alleviated Endoplasmic Reticulum Stress via Inducing ER-phagy in the Spinal Cord of Neuropathic Pain Model

“…To examine paw sensitivity in response to thermal stimulus, the TWL assay was applied as described previously (Li and Zhang, 2018). The left hind paw of the animal was exposed to a heat stimulus via automatic plantar analgesia tester (BME-410C, China).…”

Intrathecal dexmedetomidine improves epidural labor analgesia effects: a randomized controlled trial

“…Recently, Li et al. 32 demonstrated that the analgesic effect of Dex is likely associated with the inhibition of protein kinase C expression in the spinal dorsal horn. These studies indicated that the analgesic effects of Dex were not only related to α 2 ‑adrenergic receptors but also due to the direct inhibition of the signaling pathway via an α 2 ‑independent mechanism.…”

Epidural and Intrathecal Drug Delivery in Rats and Mice for Experimental Research: Fundamental Concepts, Techniques, Precaution, and Application

“…Acute needle puncture is usually used for single drug administration but can also be used for multiple doses [5], and intervals of 24 h, 2 days, and 7 days have been reported (Table 3). Acute needle puncture can be performed in anesthetized [41] or unanesthetized animals [5,42]; however, intrathecal injections in unanesthetized animals require greater skills. The intervertebral space of the spinal column is commonly used, but the lumbar region [41,43], especially L5-L6, is most commonly used for single acute injection [16,44].…”

“…Acute needle puncture can be performed in anesthetized [41] or unanesthetized animals [5,42]; however, intrathecal injections in unanesthetized animals require greater skills. The intervertebral space of the spinal column is commonly used, but the lumbar region [41,43], especially L5-L6, is most commonly used for single acute injection [16,44]. However, multiple injections were performed through a single location, e.g., L5-L6 [5,6], L4-L5 [45], and top of the foramen [46] (Table 3).…”