Tramadol relieves thermal hyperalgesia in rats with chronic constriction injury of the sciatic nerve

Abstract

The present study was designed to test whether tramadol is effective in the control of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve was induced over the left hind limb in male Sprague-Dawley rats. Identical surgery was performed on the opposite side except that the sciatic nerve was not ligated (sham surgery). Paw withdrawal latency (PWL) to heat was tested for each hind paw 1 day before surgery and on the 4th day after surgery to ensure the development of thermal hyperalgesia. In the acute treatment groups, saline or tramadol was administered subcutaneously at doses of 10, 20 or 30 mg/kg, and PWLs were measured 30, 60, 90, 120, 150 and 180 min after treatment. In the semi-chronic treatment groups, continuous systemic administration of tramadol 40 mg/kg/day or saline for 7 days was provided at a uniform rate via osmotic mini pumps. Tramadol reversed PWL in a dose-dependent manner in the acute treatment groups. PWLs were significantly reversed at 2 days after tramadol infusion, and this effect was sustained throughout the remainder of the treatment period in comparison with the saline group. Tramadol also resulted in a decreased sensitivity to thermal stimulus on the sham limb both in acute and semi-chronic administration. We conclude that both acute and semi-chronic tramadol treatment relieves thermal hyperalgesia effectively in rats with CCI of the sciatic nerve. This indicates that tramadol shows promise as a potential treatment for relief of neuropathic pain in humans.

Is the Second Phase of the Formalin Test Useful to Predict Activity in Chronic Constriction Injury Models? A Pharmacological Comparison in Different Species

“…In the literature, we found a good correlation with these data for (1) μ opioid agonists, which show activity in both species and both test conditions, 28–35 only codeine shows a lower activity in the gerbil because the conversion from codeine to morphine is much slower; 36 (2) the α2 agonists; 19 the NMDA antagonists; 37–40 (4) baclofen; 41–43 (5) the tricyclic antidepressant; 44 (6) the antiepileptic/anticovulsant: carbamazepine demonstrates only a partial effect 41,45–49 whereas gabapentin is active in the formalin, but less in the CCI model, normally higher doses are needed to see clinical relevant effects; 50 (7) the non‐steroidal anti‐inflammatory drugs are active in the CCI model; 51 and (8) the tachykinin NK antagonists are more active in the CCI model than in the second phase of the formalin test, the NK‐1 demonstrates better effect than NK‐3 52–56 …”

Preventive and Alleviative Effect of Tramadol on Neuropathic Pain in Rats: Roles of α2-Adrenoceptors and Spinal Astrocytes

“…Furthermore, the lower analgesic tolerance and dependence found in clinical (23,24) and pre-clinical studies (25) suggest that tramadol may be appropriate for long-term use such as for the treatment of neuropathic pain. However, although the acute analgesic effect of tramadol has been extensively investigated (26 -29), the long-term effect of this drug on neuropathic pain has not been well clarified (30). In addition, it has not been determined whether repeated administration of tramadol could affect spinal glial cell activation in models of neuropathic pain.…”

Tramadol in Neuropathic Pain After Spinal Cord Injury

“…12 The reason behind the sometimes high withdrawal rates can be linked to the complexity of an SCI, but in our study, withdrawal was nearly always linked to adverse events. 12 The reason behind the sometimes high withdrawal rates can be linked to the complexity of an SCI, but in our study, withdrawal was nearly always linked to adverse events.…”

“…Tramadol has been approved for treating moderate to severe acute and chronic pain in Sweden since 1995. 11 Tramadol has also been shown to be effective in decreasing suggested nociceptive-related behavior 12 (ie, thermal hyperalgesia) and in increasing nociceptive pressure thresholds in rats with a peripheral nerve lesion. 10 The authors found 4 placebo-controlled studies that evaluated the effect of tramadol in neuropathic pain and concluded that tramadol is an effective treatment for neuropathic pain.…”