Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats

Abstract

The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

“…The mean±SD AUC values obtained after administration of amitriptyline and doxepin nanoparticles were higher than those obtained for its respective solutions, resulting in a significant increase (p<0.05) of 77 and 229%, respectively. As previously observed for similar formulations [29], these increases were higher than that found in the antinociceptive experiments, specially for doxepin, probably because noxious thermal stimuli is thought to be mediated through high-threshold, thin unmyelinated primary afferent C-fibers, while non-noxious tactile stimulation is believed to be mediated through large diameter, low-threshold A afferent fibers, and processed at supraspinal sites receiving input through the dorsal column [55]. This latter path may be more potently blocked by increasing in time the presence of these drugs in the organism.…”

Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation

“…Although mechanisms of allodynia are not entirely understood, they may involve A-beta myelinated afferents [25], activated microglia and astrocytes [26-30], and dorsal horn neuron cells [28]. It has been shown that sodium channel blockers applied to the injured site [31], DRG [32] or the spinal cord [33] all effectively decrease neuropathic pain and attenuate hyperalgesia and allodynia. The present study demonstrates that intrathecal pretreatment with amitriptyline, a sodium channel blocker, enhances the effect of systemic amitriptyline on mechanical and thermal hypersensitivity when compared to systemic administration alone.…”

Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3expression and decreasing spinal microglial activation

“…Although the exact roles of activated spinal microglia and neurons in pain processing are still undetermined, an increase in p-p38 levels in activated microglia after peripheral nerve injury is reported to be a major cause of hypersensitivity to pain [28-30]. Intrathecal administration of lidocaine after peripheral nerve injury is known to reverse well-developed tactile allodynia [14]. A rat model of chronic constriction injury also indicated that lidocaine reverses tactile allodynia by attenuating phosphorylation of p38 in spinal cord microglia [12].…”

“…Intravenous administration of lidocaine also alleviates the tactile allodynia associated with neuropathic pain [11]. Intrathecal lidocaine after peripheral nerve injury reverses well-developed tactile allodynia either through interaction with eicosanoid systems in the spinal dorsal horn or by attenuating phosphorylation of p38 mitogen-activated protein (MAP) kinase in activated microglia of the spinal cord [12-14]. However, the use of intrathecal lidocaine pretreatment to attenuate neuropathic pain is not a recognized therapeutic option.…”