Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion

Abstract

Background/Aims: Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA. Methods: Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot. Results: After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression. Conclusions: Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

Key Developments in the Potential of Curcumin for the Treatment of Peripheral Neuropathies

“…Chronic constriction injury models treated with curcumin had reduced promoter acetylation and subsequent reduced expression of BDNF and Cox-2 in the spinal cord [ 53 ]. The decrease in expression paired with behavioral findings of lower threshold for mechanical, heat, and cold allodynia provides support for curcumin’s anti-nociceptive effects via its anti-inflammatory pathways [ 53 , 60 ].…”

“…Thus, in particular by its anti-inflammatory action, curcumin reduced mechanical and thermal hypersensitivity in the CCI model in SD rats [ 53 , 54 , 55 ], in Wistar rats [ 56 ], in male C57BL/6J mice [ 57 ], and in nerve ligature model in female Wistar rats [ 58 ] and in BALB/c mice [ 59 ]. Finally, curcumin also showed antinociceptive properties in SD rats in models of brachial plexus avulsion [ 60 ], alcohol-induced neuropathy in male and female Wistar rats [ 61 , 62 ], opioid-induced hyperalgesia in C57-BL/6J mice [ 63 ], HIV-gp120-induced neuropathic pain in male SD rats [ 64 ], and complete Freund’s adjuvant-induced inflammatory pain in Charles-Foster strain rats [ 65 ].…”

“…Unphosphorylated IκB-α binds to NF-κB and prevents its translocation to the nucleus, thus inhibiting downstream expression and release of cytokines [ 86 ]. Similarly, in vivo studies have shown curcumin to dose-dependently downregulate the expression of INF-γ [ 87 ], TNF-α [ 39 , 43 , 60 , 61 , 67 , 87 , 88 ], IL-1β [ 39 , 61 , 87 ], IL-17 [ 87 ], IL-6 [ 39 , 61 , 87 ], and C-reactive protein [ 67 ]. This downregulation of cytokines is seen systemically in the sciatic nerve, whole brain, and spinal cord samples of autoimmune neuritis, alcoholic neuropathy, sciatic nerve injury, chemotherapy-induced peripheral neurotoxicity, and various rodent models used in the studies above.…”

“…This downregulation of cytokines is seen systemically in the sciatic nerve, whole brain, and spinal cord samples of autoimmune neuritis, alcoholic neuropathy, sciatic nerve injury, chemotherapy-induced peripheral neurotoxicity, and various rodent models used in the studies above. Nerve growth factor (NGF), c-Fos [ 60 ], brain-derived neurotrophic factor (BDNF) [ 53 ], and Cox-2 [ 53 ] are some markers for inflammation-mediated pain [ 60 ]. As curcumin has the capacity to reduce the inflammatory response, spinal cord expression of both NGF and c-Fos was reduced in a brachial plexus avulsion model [ 60 ].…”

“…Nerve growth factor (NGF), c-Fos [ 60 ], brain-derived neurotrophic factor (BDNF) [ 53 ], and Cox-2 [ 53 ] are some markers for inflammation-mediated pain [ 60 ]. As curcumin has the capacity to reduce the inflammatory response, spinal cord expression of both NGF and c-Fos was reduced in a brachial plexus avulsion model [ 60 ]. The assumption is that the NGF measured was pro-NGF, since this is the form of NGF involved in neuronal apoptosis and death [ 78 ].…”