Behavioral and Morphological Evidence for the Involvement of Glial Cells in the Antinociceptive Effect of Najanalgesin in a Rat Neuropathic Pain Model

Abstract

Neuropathic pain is a devastating neurological disease that seriously affects patients' quality of life. Despite a high level of incidence, the underlying mechanisms of neuropathic pain are still poorly understood. However, recent evidence supports the prominent role of spinal glial cells in neuropathic pain states. In our laboratory, we observed that najanalgesin, a novel peptide isolated from the venom of Naja naja atra, exerts significant analgesic effects on acute pain in mice and neuropathic pain in rats. The objective of the present study was to determine whether spinal glia are associated with the antinociceptive effect of najanalgesin in an L5 spinal nerve ligation (SNL) rodent model of neuropathic pain. Mechanical allodynia developed after surgery, and hypersensitivity was significantly attenuated by the intrathecal administration of najanalgesin. The inhibitory effect of najanalgesin was significantly (p<0.05) enhanced after pretreatment with fluorocitrate (a glial cell antagonist). In addition, the astrocyte activation was attenuated following najanalgesin treatment in the dorsal horn of neuropathic rats, as assessed by immunohistology and Western blotting. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) content of cerebral spinal fluid and cell culture supernatants changed significantly after najanalgesin administration. The results suggest that najanalgesin may exert its anti-allodynic effect by altering astrocyte cell function.

The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective

“…The cytokine TNFα is elevated in spinal cord of human inflammatory neuropathy (105). Such increases in TNFα are also found in nerve-ligated rats (111, 112). These findings support the role of inflammatory factors in chronic pain.…”

The Effect of Bone Marrow–Derived Mesenchymal Stem Cell Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta-Analysis

“…In the last 2 decades, stem cell transplantation has been considered a possible therapeutic method for the spinal cord injury and neuropathic pain conditions [6,[9][10][11][12][13]. Mesenchymal stem cells are the main source of cell therapy because of their ability of differentiating into multiple cell types, including blood, adipose tissue, connective tissues, osteocytes, chondrocytes, hepatocytes, myocytes, neurons, and cardiomyocytes [14][15][16].…”

Antinociceptive Effect of Najanalgesin from Naja Naja Atra in a Neuropathic Pain Model via Inhibition of c-Jun NH2-terminal Kinase

“…In addition, we have observed that astrocytes were involved in the antinociception of najanalgesin during the maintenance of pain in the previous study. [ 7 ] Therefore, the effect of najanalgesin may act through the JNK signaling pathway in the spinal cord on the maintenance of neuropathic pain.…”

“…Mechanical sensitivity was assessed using the up-down method as previously described using a set of von Frey hairs (Ugo Basile, Italy). [ 6 7 ]…”

“…Immunohistochemistry was performed on 25-μm free-floating L5 spinal cord sections as previously described. [ 7 ] Spinal cord sections were incubated overnight at 4°C with JNK primary antibody (1:1000) and subsequently incubated with a Cyc3-conjugated secondary antibody (1:6000, Boshide, China). To assess nonspecific staining, control sections were incubated in the absence of primary antibodies.…”