Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis

Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis

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. Male Wistar rats received carrageenan and LPS in the right...

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Bibliographic Details
Published in:Life sciences (1973) Vol. 236; p. 116860
Main Authors: Lucena, Flora, Callado de Oliveira, Débora M.M., Norões, Maíra M., Mujica, Elba M.M., Melleu, Fernando F., Benedet, Patrícia de O., Stein, Taciane, Ribeiro, Lucineia F.C., Tonussi, Carlos R.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 01-11-2019
Elsevier BV
Subjects:
Analgesia
Analgesics
Arthritis
Bumetanide
c-Fos protein
Capsaicin receptors
Carrageenan
Cell adhesion & migration
Chloride transport
Damage prevention
Dorsal horn
Dorsal root reflex
Edema
Fos protein
Histology
Immunohistochemistry
Injection
Intrathecal injection
Joints (anatomy)
Knee
Leukocyte migration
Leukocytes
Lipopolysaccharides
Morphine
Narcotics
Neurogenic inflammation
Neurotoxins
Opioid
Opioid receptors
Pain perception
Resiniferatoxin
Rodents
Spinal cord
Synovial fluid
Toxins
Tramadol
Tumor necrosis factor-α
Opioid
Intrathecal injection
Spinal cord
Arthritis
Neurogenic inflammation
Dorsal root reflex
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Summary: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. 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. 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. 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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2019.116860