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Recent studies have shown that mesenchymal stem cells (MSCs) and their conditioned medium (CM) have potential therapeutic effects in animal models of neuropathic pain (NP). However, the mechanisms underlying these effects are not fully understood. Because of the leading involvement of purinergic receptors in the pathogenesis of NP, this study aimed to investigate the effect of MSCs-CM on the expression levels of P2X4 and P2X7 receptors in a rat model of NP induced by chronic constriction injury (CCI) of the sciatic nerve. CM was prepared from the rats' bone marrow-derived MSCs culture. After that, NP rats were treated by intraperitoneal injection of CM, or Dulbecco's modified Eagle's medium (DMEM) 1 day before and 7 and 11 days after CCI surgery. The NP status was assessed in the treated animals using behavioral tests, including mechanical allodynia and thermal hyperalgesia, on days - 1, 3, 6, 9, 12, and 15 of the study. At the end of the study (Day 15), the animals were sacrificed, and the relative gene expression of P2X4 and P2X7 receptors were measured in the spinal cord using quantitative real-time PCR. The results demonstrated that in the CM-treated NP rats, mechanical allodynia and thermal hyperalgesia were significantly reduced compared with the DMEM-treated group. In addition, the expression levels of P2X4 and P2X7 receptors were noticeably prevented in the CM-treated group than the control group. These findings indicate that the antinociceptive effects of CM in the NP rats are partly mediated through preventing the upregulation of P2X4 and P2X7 receptors in the spinal cord.

BACKGROUND AND OBJECTIVE: Neuropathic pain is a common complication of diabetes. Today opioid analgesics such as morphine, use for the management of neuropathic pain. Since the respiratory effects of morphine have not been studied in diabetes, the aim of this study was to investigate the effect of chronic hyperglycemia on the effects of morphine on respiration. METHODS: 32 Male Wister rats were randomly allocated into control group (injection of citrate buffer as streptozotocin solvent), morphine group (injection of citrate buffer as STZ solvent and injection of morphine before respiratory recording) group, hyperglycemia group (STZ injection), and hyperglycemia-morphine group (STZ injection and morphine injection before respiratory recording). Hyperglycemia was induced by injecting streptozotocin (35 mg/kg, i.p.). Respiration was recorded by plethysmography after which respiratory volume, inter-breath interval, and respiratory rate were quantified using MATLAB. FINDINGS: Mean of respiratory rate (in the hyperglycemia was 83±3.9 and control was 101±4 (p<0.05)), coefficient of variation of respiratory rates (in the hyperglycemia was 0.615±0.1 and control was 1.05±0.07 (p<0.05)), mean of respiratory volume (in the hyperglycemia was 1.44±0.19 and was control 1.1±0.11 (p<0.05)), and mean of inter-breath interval (in the hyperglycemia was 1.28±0.01 and control was 0.93±0.03 (p<0.05)). coefficient of variation of respiratory volumes (in the hyperglycemia-morphine was 1.14±0.16 and was morphine was 1.68±0.1 (p<0.05)), mean of respiratory rate (in the hyperglycemia-morphine was 1.24±0.34 and morphine was 0.37±0.04 (p<0.05)), and mean of inter-breath interval (in the hyperglycemia-morphine was 1.09±0.07 and morphine was 0.74±0.05 (p<0.01)). CONCLUSION: Our results show that chronic hyperglycemic changed breathing pattern and respiratory response to morphine. [ABSTRACT FROM AUTHOR]