Effect of pioglitazone on neuropathic pain and spinal expression of TLR-4 and cytokines

Abstract

Abstract. The molecular mechanisms underlying neuropathic pain have yet to be elucidated. The present study aimed to examine the modulation of neuroimmune activation in the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (Pio), in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Rats were randomly assigned into four groups: Sham surgery with vehicle, chronic constriction injury with vehicle or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-γ antagonist GW9662 (2 mg/kg). Pio or vehicle was administered 1 h prior to the surgery and continued daily until day 7 post-surgery. Paw pressure threshold was measured prior to surgery and on days 0, 1, 3 and 7 post-surgery. Microglia activation markers macrophage antigen complex-1, the mRNA expression levels of tumor necrosis factor α and interleukin-1β, and the mRNA expression levels of toll like receptor (TLR-4) in the lumbar spinal cord were determined. Administration of Pio resulted in the prominent attenuation of mechanical hyperalgesia. In addition, Pio was able to significantly inhibit neuroimmune activation characterized by glial activation, the production of cytokines and expression levels of TLR-4. Concurrent administration of a PPAR-γ antagonist, GW9662, reversed the effects of Pio. The antihyperalgesic effect of administration of Pio in rats receiving CCI may, in part, be attributed to the inhibition of neuroimmune activation associated with the sustaining of neuropathic pain.

miRNA‑146a attenuates inflammation in an in�vitro spinal cord injury model via inhibition of TLR4 signaling

“…TLR4 is a membrane receptor with leucine-rich repeat. As is reported in previous study, injection of lipopolysaccharide in the spinal cord can upregulate TLR4 expression and activate the inflammatory response (6). Thus, SCI has resulted in nerve injury and functional defect, which reveals that TLR4 is distributed in the spinal cord (3).…”

“…Toll-like receptor-4 (TLR4) is a pattern recognition receptor, which is closely related to congenital immunity (6). TLR4 is a membrane receptor with leucine-rich repeat.…”

Ulinastatin inhibited sepsis‐induced spinal inflammation to alleviate peripheral neuromuscular dysfunction in an experimental rat model of neuromyopathy

“…; Jia et al . ). Only a few studies have focused on CNS inflammation‐induced peripheral neuromuscular dysfunction (Dubový ).…”

“…Although the activation of microglia/macrophage in the CNS is associated with neuroinflammation, a growing number of studies have focused on either neuroinflammation-induced cognitive dysfunction or neuropathic pain (Iaccarino et al 2016;Jia et al 2016). Only a few studies have focused on CNS inflammation-induced peripheral neuromuscular dysfunction (Dubov y 2011).…”

Herbal Decoction Divya-Peedantak-Kwath Alleviates Allodynia and Hyperalgesia in Mice Model of Chemotherapy-Induced Peripheral Neuropathy via Modulation in Cytokine Response

“…PPAR agents like pioglitazone and rosiglitazone have been explored in these regards. These agents are neuroprotective (decreased lesion volume), anti-inflammatory (decreased microglial activation and inflammatory gene expression), anti-apoptotic (decreased number of apoptotic neurons), and antioxidative ( Jia et al, 2016 ). But, weight gain, fluid retention, congestive heart failure, and bone fractures are common adverse effects associated with pioglitazone and rosiglitazone ( Nesto et al, 2003 ; Betteridge, 2011 ).…”