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Introduction: The major secondary complications of spinal cord injury (SCI) are neuropathic pain and motor dysfunction, which remained medical challenges for clinicians. Due to the major role of glutamate in excitotoxicity and central sensitization, the present experiment was to evaluate the effects of ketamine (KET), an n-methyl-D-aspartate (NMDA) receptor blocker, on sensory-motor functions in a rat model of clip compression SCI. Methods: Wistar rats were divided into sham, SCI and KET-treated groups. The sham group received laminectomy without any compression lesion. KET and SCI groups were subjected to severe compression injury for 1min with an aneurysm clip and then treated with KET (10mg/kg) or 5% dimethyl sulfoxide (as vehicle), respectively. The rats were assessed by pain-related and motor behavioral tests inclusive of von Frey, acetone drop, hot plate, inclined plane and Basso-Beattie-Bresnahan on day 0 prior to the injury and the 7th, 14th, 21st and 28th days following SCI. Results: KET group compared with the SCI group showed a significant decline in the mechanical allodynia on the 21st and 28th days, and in cold allodynia from the 1st week to the 4th week post-injury. KET treatment improved the motor function but not weight loss and auricle temperature rise during the 4 weeks of follow up from the 1st week until the 4th week. Conclusion: It was ultimately attained that the advantageous effects of intrathecal KET on sensory-motor dysfunction of SCI rats could provide new approaches for KET as a neuroprotective agent toward clinical applications. [ABSTRACT FROM AUTHOR]

Objective(s): Neuropathic pain is a prevalent and debilitating neurological disorder. Ample evidence indicates that microglial cells and inflammatory cytokines are involved in the pathogenesis of neuropathic pain. Alpha-terpineol is a monoterpenoid alcohol with inhibitory effect on inflammatory cytokines. The main purpose of this study was to evaluate the effect of α-terpineol on neuropathic pain in rats. Materials and Methods: Chronic constriction injury (CCI) model was utilized to induce neuropathic pain in male Wistar rats. The rats were randomly divided into control, sham, α-terpineol, and gabapentin groups. Normal saline, α-terpineol (25, 50, and 100 mg/kg), and gabapentin (100 mg/kg) were administered intraperitoneally in the above-mentioned groups once daily for 14 days post-CCI. Behavioral tests, including Von Frey, acetone, and Hargreaves were used to assess mechanical allodynia, cold allodynia, and hyperalgesia in rats. Iba1 immunostaining and ELISA procedures were used to assess the activation of microglial cells and inflammatory cytokines level. Results: The results showed that α-terpineol (50 and 100 mg/kg) significantly attenuated mechanical allodynia, cold allodynia, and hyperalgesia in the neuropathic rats. The analgesic effect of α-terpineol (100 mg/kg) was comparable with that of gabapentin as a standard antineuropathic pain drug. In addition, α-terpineol (25, 50 and 100 mg/kg) significantly decreased the number of Iba1-positive cells and diminished the concentration of IL-1β and TNF-α in the spinal tissue. Conclusion: It was ultimately attained that α-terpineol attenuates neuropathic pain through the suppression of the microglial cells and reduction of inflammatory cytokine levels in the spinal cord of rats. [ABSTRACT FROM AUTHOR]

Cuminic alcohol (4-isopropylbenzyl alcohol; 4-IPBA) is a monocyclic terpenoid found in the analgesic medicinal plants Cuminum cyminum and Bunium persicum. The current study assessed the analgesic effects of 4-IPBA in different animal models of pain. Hot plate, formalin, and acetic acid tests were used to evaluate nociceptive pain in mice. The involvement of opioid receptors and the L-arginine/NO/cGMP/K+ channel pathway in 4-IPBA effects were investigated. Allodynia and hyperalgesia were assessed following peripheral neuropathy induced by chronic constriction of the sciatic nerve in rats. The spinal levels of inflammatory cytokines were measured using the ELISA method. The drugs and compounds were administered intraperitoneally. The results showed that 4-IPBA (200 and 400 mg/kg) significantly prolonged the hot plate latency. This effect was antagonized by naloxone (2 mg/kg). 4-IPBA (25–100 mg/kg) also significantly attenuated formalin- and acetic acid-induced nociceptive pain. L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg) reversed while L-NAME (30 mg/kg) and methylene blue (20 mg/kg) potentiated the antinociceptive effects of 4-IPBA in the writhing test. Glibenclamide (10 mg/kg) and tetraethylammonium chloride (4 mg/kg) did not have any influence on the 4-IPBA effect. Furthermore, 4-IPBA (6.25–25 mg/kg) significantly relieved mechanical allodynia, cold allodynia, and hyperalgesia in rats. The concentrations of TNF-α and IL-1β in the spinal cord of rats were decreased by 4-IPBA. No evidence of 4-IPBA-induced toxicity was found in behavioral or histopathological examinations. These results demonstrate that 4-IPBA attenuates nociceptive and neuropathic pain through the involvement of opioid receptors, the L-arginine/NO/cGMP pathway, and anti-inflammatory functions. [Display omitted] • Research highlights: • Cuminic alcohol attenuates nociceptive and neuropathic pains. • Cuminic alcohol exerts its antinociceptive effect through opioid receptors. • L-arginine/NO/cGMP pathway is involved in cuminic alcohol effects. • Cuminic alcohol suppresses inflammatory cytokines in the spinal cord. [ABSTRACT FROM AUTHOR]

In Iranian traditional medicine, Cuminum cyminum is a unique medicinal herb for pain relief. Cuminaldehyde has been distinguished as the major constituent of C. cyminum seeds; even though, the analgesic effect of cuminaldehyde has not yet been examined. The nobility of this study was to assess cuminaldehyde effect on nociceptive and neuropathic pains; furthermore, evaluation of its possible mechanisms of action. Hot plate, formalin, and acetic acid-induced writhing tests were used to evaluate nociception in mice. Naloxone (opioid receptors antagonist), L-arginine (nitric oxide (NO) precursor), L-NAME (NO synthase inhibitor), sodium nitroprusside (NO donor), methylene blue (guanylyl cyclase inhibitor), sildenafil (phosphodiesterase inhibitor), and glibenclamide (K ATP channel blocker) were used to determine the implication of opioid receptors and L-arginine/NO/cGMP/K ATP channel pathway. Allodynia and hyperalgesia were investigated in the CCI (chronic constriction injury) model of neuropathic pain in rats. The ELISA method was used to measure the inflammatory cytokines in serum samples of rats. The entire chemicals were intraperitoneally injected. Cuminaldehyde (100 and 200 mg/kg) significantly decreased the latency to nociceptive response in the hot plate test. The outcome of cuminaldehyde was completely antagonized by naloxone (2 mg/kg). Formalin- and acetic acid-induced nociception was significantly inhibited by cuminaldehyde (12.5–50 mg/kg). The antinociceptive effect of cuminaldehyde was reversed in writhing test by L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg); however, L-NAME (30 mg/kg) and methylene blue (20 mg/kg) enhanced the effect of cuminaldehyde. Glibenclamide (10 mg/kg) did not alter the antinociceptive effects of cuminaldehyde. In the CCI-induced neuropathy, cuminaldehyde (25–100 mg/kg) significantly alleviated allodynia and hyperalgesia and decreased the serum levels of TNF-α and IL-1β. It was attained magnificently that cuminaldehyde exerts antinociceptive and antineuropathic effects through the involvement of opioid receptors, L-arginine/NO/cGMP pathway, and anti-inflammatory function. Image 1 • Cuminaldehyde attenuates nociceptive and neuropathic pains. • Opioid receptors are implicated in antinociceptive effect of cuminaldehyde. • L-Arg/NO/cGMP pathway plays an important role in the cuminaldehyde effect. • Cuminaldehyde alleviates pain via suppression of inflammatory cytokines. [ABSTRACT FROM AUTHOR]