Enhancement of imipramine-induced antinociception by transcutaneous electrical nerve stimulation in formalin test

Acute and chronic pain physically and psychologically disables an overwhelming number of people and it is the most common reason that they consult physicians. Therefore, many pharmacological and non-pharmacological interventions have been found to be effective in managing pain. This study investigates the interference of imipramine and transcutaneous electrical nerve stimulation (TENS) on inflammatory pain response induced by formalin in adult Wistar rats.

Rats were divided into 15 groups; six rats in each group. First, imipramine was administrated intraperitoneally and after 15 min intra-plantar formalin injection occurred. In combination groups, immediately after formalin injection, different frequencies of TENS were applied on left limb of rats in formalin test task. Simultaneous with TENS, nociceptive responses were quantified in a biphasic reaction including acute and chronic phases in formalin test method.

Intraperitoneal administration of imipramine (2.5-10 mg/kg) produced a dose-dependent antinociception in both the first and second phases of formalin test in mice. The antinociceptive response was observed at the maximum dose of the drug. However, application of TENS, immediately after formalin injection, at the frequencies of 1, 3, 20 or 1, 3, 20, 100 Hz induced antinociception in acute or chronic phase of formalin test, respectively. Furthermore, applied TENS at a low and sub-effective frequency (0.3 Hz) decreased imipramine response at two lower doses in acute phase and potentiated imipramine effect at the higher dose in chronic phase.

It is concluded that combination of imipramine and TENS may be effective for treatment of pain. To decline the adverse effects of the medications and use them at the low doses, combined interventions both pharmacological and non-pharmacological strategies for pain treatment are suggested.