Effects of lacosamide, a novel sodium channel modulator, on dorsal horn neuronal responses in a rat model of neuropathy

Background Cancer-induced bone pain is a major clinical problem for which current treatments lack full efficacy. Gabapentin is licensed for use in neuropathic pain yet is also effective against inflammatory stimuli in animals. Methods A rat model of cancer-induced bone pain using the MRMT-1 cell line injected into the tibia was established to investigate the efficacy of acute (10, 30, 100 mg/kg) and chronic (30 mg/kg) systemic gabapentin on electrophysiological superficial dorsal horn neuronal responses to natural and noxious electrical stimuli, as well as on pain-related behavior. Results In electrophysiological studies gabapentin worked both acutely (100 mg/kg) and chronically (30 mg/kg) to normalize the hyperexcitable superficial dorsal horn neuronal response, significantly reducing electrical-evoked and mechanical-evoked but not thermal-evoked responses. The behavioral study showed that chronic gabapentin (30 mg/kg) significantly attenuated pain behavior in MRMT-1 rats, restoring responses to preoperative baseline degrees, and that this attenuation was accompanied by a reversion to normal (non-MRMT-1) wide-dynamic-range: nociceptive specific superficial dorsal horn neuronal profiles. Conclusions Pain-related behavior in this rat model of cancer-induced bone pain is strongly linked to hyperexcitability of a population of superficial dorsal horn neurones. Gabapentin normalizes the cancer-induced bone pain induced dorsal horn neuronal changes and attenuates pain behavior. It may therefore provide a novel clinical treatment for cancer-induced bone pain.

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Superficial dorsal horn neuronal responses and the emergence of behavioural hyperalgesia in a rat model of cancer-induced bone pain

Neuroscience Letters ◽

10.1016/j.neulet.2004.01.048 ◽

2004 ◽

Vol 360 (1-2) ◽

pp. 29-32 ◽

Cited By ~ 25

Author(s):

T Donovan-Rodriguez ◽

A.H Dickenson ◽

C.E Urch

Keyword(s):

Dorsal Horn ◽

Rat Model ◽

Bone Pain ◽

Superficial Dorsal Horn ◽

Neuronal Responses

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Sini-San Regulates the NO-cGMP-PKG Pathway in the Spinal Dorsal Horn in a Modified Rat Model of Functional Dyspepsia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3575231 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Zhenyu Wu ◽

Xiaofang Lu ◽

Shengsheng Zhang ◽

Chunyang Zhu

Keyword(s):

Gene Expression ◽

Dorsal Horn ◽

Functional Dyspepsia ◽

Rat Model ◽

Spinal Dorsal Horn ◽

Visceral Hypersensitivity ◽

Enzyme Linked Immunosorbent Assay ◽

Gastric Distention ◽

Real Time Quantitative Pcr ◽

Spinal Dorsal

The present study investigated the effect of Chinese medicine Sini-San (SNS) on visceral hypersensitivity in a rat model of functional dyspepsia (FD), and it explored related underlying mechanisms. The rat model of FD was developed by combining neonatal iodoacetamide (IA) treatment and adult tail-clamping. After SNS treatment, the behavior and electromyographic testing were performed to evaluate the visceromotor responses of rats to gastric distention. Immunofluorescence was used to detect the distribution of iNOS-positive cells in the spinal dorsal horn, while the real-time quantitative PCR and western blot were used for detection of the gene expression of c-fos, iNOS, and GABAb and protein levels of iNOS and GABAb in the spinal dorsal horn, respectively. The protein concentration of cGMP and PKG proteins in the spinal dorsal horn were quantified by enzyme-linked immunosorbent assay. In this study, SNS treatment significantly reduced the behavioral score and electromyographic response to graded intragastric distension pressure. The middle-dose of SNS treatment significantly reduced the distribution of iNOS-positive cells in the spinal dorsal horn of FD model rats. The gene expression of c-fos, iNOS, and GABAb and the protein contents of iNOS, GABAb, cGMP, and PKG in the spinal dorsal horn of FD model rats were restored to a normal level by middle-dose of SNS treatment. Our results suggest that Sini-San may alleviate the visceral hypersensitivity in FD model rats via regulation of the NO/cGMP/PKG pathway in the spinal dorsal horn.

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