The Effect of Acute Intra Locus Coeruleus (LC) Microinfusion of Bupropion on Formalin-Induced Pain Behavior in Rat

Introduction: Inflammatory pain is a common sign of chronic diseases. Some brain regions such as locus coeruleus (LC) of the brainstem nor-epinephrine (NE) system have a key role in The mechanisms of the pain modulation and dependence. Bupropion synthesized as an antidepressant, but it is using for smoke cessation. It can change morphine withdrawal signs such as pain related behaviors. This study tested the acute effect of intra-LC microinfusion of bupropion on the formalin-induced pain behavior in rats.  Methods: Wistar male rats were divided into 6 groups (control-naïve, control-operated, shamoperated, and 3 treated groups with 10-2, 10-3, 10-4 mol/&mul intra-LC of bupropion). The injection guide cannulae were implanted into LC nuclei bilaterally by stereotaxic coordinated surgery under sterile condition. The sham group received normal saline as drug vehicle but control groups had no intra-LC injections. Formalin (50 &mul, 2.5%) was injected subcutaneously in plantar region of the right hindpaw in all animals (30 min after drug administration in treated animals). Nociceptive signs were observed continuously and registered on-line each minute. Common pain scoring was used for pain assessment.  Results: The analysis of data by one-way ANOVA showed that bupropion can reduce pain behavior scores significantly. Bupropion reduced total pain score in the phase 01 (60%) and phase 02 (52%) of maximal behavior compared to the sham group, dose dependently and significantly. The pain scores of controls and sham groups had no significant difference.  Discussion: The results showed that bupropion has analgesic effects on LC neurons and can alter the neurochemical involvement of LC in pain process. Bupropion has different and significant effect on early and late phases of formalin test.