The analgesic effect of total saponins of Tribulus terrestris on neuropathic pain was studied based on TLR4/NF-κB pathway

Neuropathic pain (NP) consists of a range of unpleasant sensations attributed to a lesion or a disease of the somatosensory nervous system. It is important to note that the sensations initiated by NP are debilitating and adversely affect quality of life; however, the underlying mechanisms involved in the occurrence and development of this type of pain remain to be determined. Previously data demonstrated that inhibition of TLR4/NF-κB signaling pathway diminished the adverse consequences attributed to NP. Thus, the purpose of this study was to examine whether saponins derived from <i>Tribulus terrestris</i> might exert an analgesic effect on NP in rats using a chronic constriction injury (CCI) involving sciatic nerve. Male rats were randomly divided into Sham, CCI, low 100 mg/kg <i>T. terrestris</i>, high 200 mg/kg <i>T. terrestris</i>, and compared to pregabalin 10 mg/kg, the recognized first line of defense in NP. Three days after surgery, rats were treated with sham control (water) or drugs. The paw mechanical withdrawal threshold (PMWT) and thermal latency (TL) of rats were measured 1 day before operation and 3, 7, and 10 days after. Nissl staining was used to observe the morphology and Western Blot to detect protein expression of NF-κB and TLR4 on the 10th day after operation. ELISA was employed to detect levels of IL-1β, IL-6, and TNF-ɑ in spinal cord. CCI significantly decreased PMWT and TL. In CCI neurons and glial cells in the spinal dorsal horn were deeply stained with swelling and atrophy observed. The protein expression levels of NF-κB and TLR4 in the spinal dorsal horn of the injured side were significantly increased accompanied by elevated levels of inflammatory mediators IL-1β, IL-6, and TNF-ɑ. Treatment with low 100 mg/kg or high 200 mg/kg <i>T. terrestris</i> or pregabalin reduced effects of CCI on PMW, TL, histopathological changes as well as levels of inflammatory cytokines IL-1β and IL-6 associated with inhibition of TLR4/NF-κB pathway. Data suggest that <i>T. terrest</i> exerts an analgesic effect on peripheral NP which involves TLR4/NF-κB pathway inhibition.