Effects of intermedin on dorsal root ganglia in the transmission of neuropathic pain in chronic constriction injury rats

Summary Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. The P2X 3 receptor plays a crucial role in facilitating pain transmission. Intermedin ( IMD ), which is also known as adrenomedullin 2 ( AMD 2) is a newly discovered hormone that is a member of the calcitonin/calcitonin gene‐related peptide family. The present research investigates the effects of IMD on pain transmission in neuropathic pain states as mediated by P2X 3 receptors in dorsal root ganglia ( DRG ). Chronic constriction injury ( CCI ) rats were used as the neuropathic pain model. Adult male Sprague‐Dawley rats were randomly assigned to five groups as follows: blank control group (Control), sham operation group (Sham), CCI rats treated with saline group ( CCI + NS ), CCI rats treated with IMD 1–53 group ( CCI + IMD 1–53 ), and CCI rats treated with IMD inhibitor IMD 14–47 group ( CCI + IMD 14–47 ). The mechanical withdrawal threshold ( MWT ) was tested by the von Frey method, and the thermal withdrawal latency ( TWL ) was tested via automatic thermal stimulus instruments. Changes in the expression of P2X 3 receptors and IMD in CCI rat L4/L5 DRG were detected using immunohistochemistry, reverse transcription‐polymerase chain reaction, and Western blotting. After treatment with intrathecal injection (i.t.), mechanical and thermal hyperalgesia in the CCI + IMD 1–53 group was maintained , but MWT and TWL in the CCI + IMD 14–47 groups increased. The expression levels of P2X 3 receptors and IMD in L4/L5 DRG in the CCI + NS and CCI + IMD 1–53 groups were significantly increased compared with those in the Control group or the Sham group. After application of IMD 14–47 in CCI rats , there was a decrease in the expression levels of P2X 3 receptors and IMD in L4/L5 DRG . The phosphorylation of p38 and ERK 1/2 in L4/L5 DRG in the CCI + NS group and the CCI + IMD 1–53 group was stronger than that in the Control group or the Sham group; however, the phosphorylation of p38 and ERK 1/2 in the CCI + IMD 14–47 group was much lower than that in the CCI + NS group or the CCI + IMD 1–53 group. Our findings indicate that IMD might increase the sensitization effects of IMD on P2X 3 receptors to alleviate chronic neuropathic pain injury. The IMD agonist IMD 1–53 might enhance nociceptive responses mediated by P2X 3 receptors in neuropathic pain, and the IMD inhibitor IMD 14–47 could inhibit the sensitization of the P2X 3 receptor in chronic neuropathic pain injury.