Effect of autophagy on allodynia, hyperalgesia and astrocyte activation in a rat model of neuropathic pain

Abstract

Primary damage or dysfunction of the nervous system may cause or initiate neuropathic pain. However, it has been difficult to establish an effective treatment for neuropathic pain, as the mechanisms responsible for its pathology remain largely unknown. Autophagy is closely associated with the pathological process of neurodegenerative diseases, neuropathic injury and cancer, among others. The aim of the present study was to examine the changes in the autophagy-lysosomal pathway and discuss the effects of autophagy on allodynia, hyperalgesia and astrocyte activation in neuropathic pain. A neuropathic pain model was induced by chronic constriction injury (CCI) in rats. Inducers and inhibitors of autophagy and lysosomes were used to assess autophagy, allodynia, hyperalgesia and astrocyte activity. Neuropathic pain was found to induce an increase in the levels of the autophagy-related proteins, LC3II and Beclin 1 and, and in those of the lysosomal proteins, lysosomal-associated membrane protein type 2 (LAMP2) and Ras-related protein Rab-7a (RAB7), whereas p62 levels were found to decrease from day 1 to 14 following CCI. The autophagy inducer, rapamycin, further increased the LC3II, Beclin 1, lysosomal-associated membrane protein 2 (LAMP2) and Ras-related protein Rab-7a (RAB7) expression levels, and decreased the p62 expression levels, which were accompanied by alleviation of allodynia, hyperalgesia and astrocyte activation in the rats subjected to CCI; the autophagy inhibitor, 3-methyladenine, reversed these effects. The use of the lysosomal inhibitors, bafilomycin and chloroquine, resulted in the accumulation of LC3II and Beclin 1, a decrease in the levels of LAMP2 and RAB7, and the exacerbation of allodynia, hyperalgesia and astrocyte activation in rats with neuropathic pain. On the whole, the findings of this study indicate that neuropathic pain activates autophagy, which alleviates mechanical and thermal hyperalgesia and suppresses astrocyte activity. Therefore, neuropathic pain induced by CCI in rats appears to be mediated via the autophagy-lysosomal pathway.

Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury

“…Wipi2, which is involved in autophagy in DRG neurons (Stavoe et al, 2019), a process 281 argued to reduce the pain associated with sciatic nerve injury (Chen et al, 2018). PEP1 282 neurons selectively induce Ano1, which promotes pain hypersensitivity (Lee et al, 2014).…”

Rab27a Contributes to the Processing of Inflammatory Pain in Mice

“…In a previous study, we found that Rab7 contributes to the processing of inflammatory pain in a redox-dependent manner [ 6 ]. Moreover, expression of Rab7 is upregulated after peripheral nerve injury [ 7 ] and Rab7-mediated lysosomal targeting of µ-opioid receptors leads to a loss in opioid antinociception in diabetic neuropathic pain [ 8 ]. Furthermore, trafficking of the neurokinin 1 receptor (NK1R) in sarcoma virus-transformed rat kidney epithelial cells was found to be controlled by Rab5a [ 9 ] and expression of Rab23 was induced in an inflammatory pain model [ 10 ], suggesting that, also, other Rab proteins contribute to the processing of pain.…”

The Analgesic and Anxiolytic Activity of Resveratrol Mediated by Different Sub-Types of α-Adrenoceptors of Anterior Cingulate Cortex Following Neuropathic Pain in Male Rats

“…Peripheral or central nerve damage can induce neuropathic pain (1,2). Common abnormal signs of neuropathic pain are hyperalgesia (exaggerated pain perception in response to noxious), allodynia (pain perception in response to non-noxious stimuli) and psychological disorders such as anxiety (3,4). In most of the pharmacological studies along with neuropathic pain management, the effects of different compounds on these behavioral parameters are investigated (5).…”