Flora Lucena1, Débora M M Callado de Oliveira1, Maíra M Norões1, Elba M M Mujica1, Fernando F Melleu2, Patrícia de O Benedet1, Taciane Stein3, Lucineia F C Ribeiro3, Carlos R Tonussi4. 1. Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil. 2. Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil. 3. Program in Biosciences and Health, State University of Western Parana, Cascavel, PR 85819-110, Brazil. 4. Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: c.r.tonussi@ufsc.br.
Abstract
AIMS: Intrathecal injection of morphine presents analgesic and antiedematogenic effects in rats. However, it is unknown whether tramadol, which possess a mixed mechanism of action, can also produce analgesic and antiedematogenic effects similarly. MAIN METHODS: Male Wistar rats received carrageenan and LPS in the right knee joint. Tramadol (10 μg) was injected intrathecally 20 min before articular LPS injection. Incapacitation and articular edema were measured 5 h after LPS stimulation. Synovial fluid was collected for leukocyte counting and western blot analysis. Whole joint and lumbar spinal cord were also collected for histology and immunohistochemistry, respectively. Intrathecal pretreatments groups were with the NKCC1 blocker bumetanide, TRPV1 agonist resiniferatoxin, μ-opioid receptor antagonist CTOP and serotonergic neurotoxin 5,7-DHT, all previously to tramadol. KEY FINDINGS: Tramadol treatment caused the reduction of incapacitation and edema. It also reduced c-Fos protein expression in the spinal cord dorsal horn and slightly reduced TNF-α levels in synovial fluid, but neither reduced cell migration nor tissue damage. Bumetanide and resiniferatoxin prevented the analgesic and antiedematogenic effects of tramadol. CTOP prevented the analgesic and the antiedematogenic effects, but 5,7-DHT prevented only tramadol-induced analgesia. SIGNIFICANCE: Spinal NKCC1 cotransporter and peptidergic peripheral afferents seem to be important for the analgesic and antiedematogenic effects of tramadol, as well as μ-opioid receptor. However, the monoamine uptake inhibition effect of tramadol seems to be important only to the analgesic effect.
AIMS: Intrathecal injection of morphine presents analgesic and antiedematogenic effects in rats. However, it is unknown whether tramadol, which possess a mixed mechanism of action, can also produce analgesic and antiedematogenic effects similarly. MAIN METHODS: Male Wistar rats received carrageenan and LPS in the right knee joint. Tramadol (10 μg) was injected intrathecally 20 min before articular LPS injection. Incapacitation and articular edema were measured 5 h after LPS stimulation. Synovial fluid was collected for leukocyte counting and western blot analysis. Whole joint and lumbar spinal cord were also collected for histology and immunohistochemistry, respectively. Intrathecal pretreatments groups were with the NKCC1 blocker bumetanide, TRPV1 agonist resiniferatoxin, μ-opioid receptor antagonist CTOP and serotonergic neurotoxin 5,7-DHT, all previously to tramadol. KEY FINDINGS:Tramadol treatment caused the reduction of incapacitation and edema. It also reduced c-Fos protein expression in the spinal cord dorsal horn and slightly reduced TNF-α levels in synovial fluid, but neither reduced cell migration nor tissue damage. Bumetanide and resiniferatoxin prevented the analgesic and antiedematogenic effects of tramadol. CTOP prevented the analgesic and the antiedematogenic effects, but 5,7-DHT prevented only tramadol-induced analgesia. SIGNIFICANCE: Spinal NKCC1 cotransporter and peptidergic peripheral afferents seem to be important for the analgesic and antiedematogenic effects of tramadol, as well as μ-opioid receptor. However, the monoamine uptake inhibition effect of tramadol seems to be important only to the analgesic effect.