BACKGROUND AND OBJECTIVE: As a crucial micronutrient, copper ion is engaged in various biochemical pathways and affects central nervous system, pain, and inflammation. Considering the significance of pain in physical and mental condition of patients, the present study aims to find new ways to reduce pain by investigating the effect of copper chloride on thermal and chemical pain and inflammatory edema through central and peripheral administrations.

METHODS: In this empirical study, 77 male Wister rats (200–250g) were divided into 11 groups (n=7) including control group (with no treatment), sham 1 (saline, i.p) receiving 5, 10, 20 and 100 mg/kg CuCl₂ intraperitoneally (i.p), sham 2 (saline, intrathecal (i.t)) receiving 0.002mg/10µl and 0.02mg/10µl CuCl₂ intrathecally (i.t), sham 3 group receiving saline plus naloxone intraperitoneally (i.p) and the group receiving 10 mg/kg CuCl₂ plus 2 mg/kg naloxone intraperitoneally (i.p). Thermal and chemical pain and the volume of inflammatory edema were assessed using tail flick, formalin and plethysmometery tests, respectively. Elevated plus maze and rotarod tests were used to examine the side effects of CuCl₂.

FINDINGS: 10 and 20 mg/kg CuCl₂ (i.p) respectively reduced thermal pain (1.69±0.38 and 1.55±0.53) (p<0.001) and chemical pain (p<0.01) and reduced inflammatory paw edema (70.43±20.96 and 70.38±29.01) (p<0.01). However, rats receiving 100 mg/kg CuCl₂ did not survive. On the other hand, naloxone abolished the analgesic effect of CuCl2 (0.015±0.055) (p<0.001). Intrathecal administration of 0.002mg/10µl CuCl₂ had no significant effect on pain but 0.02mg/10µl CuCl₂ reduced chemical pain (p<0.01). CuCl₂ had no effect on balance and anxiety.

CONCLUSION: Since administration of naloxone as opioid receptor antagonist abolished the analgesic effect of CuCl₂, CuCl₂ may induce analgesia by increasing the sensitivity of opioid receptors to endogenous opioids.