The anti-inflammatory effect of tramadol in the temporomandibular joint of rats

Lamana, Simone Monaliza Silva; Napimoga, Marcelo Henrique; Nascimento, Ana Paula Camatta; Freitas, Fabiana Furtado; Araújo, Daniele Ribeiro de; Quinteiro, Mariana; Macedo, Cristina Gomes de; Fogaça, Carlos L.; Clemente-Napimoga, Juliana Trindade

doi:10.1016/j.ejphar.2017.04.012

Cited by 25 publications

(16 citation statements)

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“…Similarly, in animals, an analgesic effect was seen from local delivery of tramadol in the knee joint (Garlicki et al, 2006;Mert et al, 2007), in the hind paws (Sousa et al, 2008;Sawynok et al, 2013), and in the TMJ (Sipahi et al, 2015). We have also previously shown an antinociceptive effect of tramadol when injected into the rat TMJ (Lamana et al, 2017).…”

Section: Introductionsupporting

confidence: 53%

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Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Abdalla

Jain

Napimoga

et al. 2019

J Pharmacol Exp Ther

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Coated microneedles have emerged as a promising drug delivery system for inflammatory pain treatment. We have previously shown that tramadol injection into the rat temporomandibular joint (TMJ) induces an antinociceptive and anti-inflammatory effect. In this study, microneedles coated with tramadol were investigated as a platform to treat TMJ pain. Male Wistar rats were administered tramadol using an intra-TMJ injection or with microneedles coated with tramadol, followed by 1.5% formalin nociceptive challenge administered 15 minutes later. The nociceptive behavior of rats was evaluated, and their periarticular tissues were removed after euthanasia for analysis. The duration of antinociceptive effect was determined by performing the formalin challenge at different time points extending up to 6 days post tramadol administration. Microneedles coated with tramadol produced an antinociceptive effect similar to injection of tramadol into the rat TMJ. Surprisingly, tramadol delivery using coated microneedles produced a more durable antinociceptive effect lasting as much as 2 days post tramadol delivery as compared with an antinociceptive effect lasting under 2 hours from intra-TMJ injection of tramadol. The proinflammatory cytokines tumor necrosis factor-a and interleukin-1b (IL-1b) were found to be reduced, whereas the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups. In conclusion, microneedles coated with tramadol can offer a therapeutic option for pain control of inflammatory disorders in the TMJ.

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Section: Introductionsupporting

confidence: 53%

“…Cytokine Measurement in Periarticular Tissue. Periarticular tissue was isolated as described before (Lamana et al, 2017). In brief, skin covering the TMJ was removed and discarded.…”

Section: And G)mentioning

confidence: 99%

Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Abdalla

Jain

Napimoga

et al. 2019

J Pharmacol Exp Ther

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“…A possible explanation for this is that magnesium, through the activation of transient receptor potential vanilloid type 1 (TRPV1) channels ( Srebro et al, 2015 , Srebro et al, 2016b ), reduced the antihyperalgesic effect of tramadol that was effected through peripheral activation of the mu-opioid receptor and consequently, through mu-opioid receptor-specific inhibition of the TRPV1 channels via G i/o proteins and the cAMP/PKA pathway. Also, the analgesic effect of tramadol includes the direct activation of the intracellular nitric oxide/cyclic guanosine monophosphate pathway in primary nociceptive neurons ( Lamana et al, 2017 ), while magnesium, by activating the same pathway in peripheral afferent neurons, could decrease the effect of tramadol ( Srebro et al, 2015 ). According to our results, we suggest that in the primary afferent activation and peripheral sensitization (the first phase of carrageenan-induced hyperalgesiatest), magnesium reduced the analgesic effect of tramadol, whereas in the late phase of the test and central sensitization, magnesium enhanced the effect of tramadol.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of α2-adrenergic receptors has been shown to inhibit nociceptive transmission in the spinal cord through presynaptic activity, and to inhibit the release of excitatory neurotransmitters from primary afferent terminals and postsynaptic sites ( Ossipov et al, 2010 ). An additional non-opioid mechanism of the analgesic effect of tramadol is the direct activation of the intracellular nitric oxide pathway in the primary signaling nociceptive neurons ( Lamana et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Additional information regarding the interaction with tramadol are that: (1) magnesium may have a permissive effect on catecholamine actions and that it can also inhibit norepinephrine release from nerve endings ( Shimosawa et al, 2004 ), (2) that both drugs could affect the NO system, with magnesium increasing NO production ( Srebro et al, 2014a ) and tramadol directly activating the intracellular nitric oxide/cyclic guanosine monophosphate pathway in primary nociceptive neurons ( Lamana et al, 2017 ), and (3) it is possible that magnesium potentiates the effect of tramadol in pain, since it has been shown that another NMDA antagonist increased the effect of tramadol in learning via activation of NO signaling pathway in brain ( Jafari-Sabet et al, 2018 ). The potentiating effect of trace elements as adjuvant analgesics at different concentrations on an analgesic compound suggests that the analgesic effect is the consequence of the synergistic interaction between magnesium and tramadol.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

et al. 2018

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Background: Inflammatory pain is the most commonly treated clinical pain, since it develops following trauma or surgery, and accompanies rheumatic or arthritic diseases. Tramadol is one of the most frequently used opioid analgesics in acute and chronic pain of different origin. Magnesium is a widely used dietary supplement that was recently shown to be a safe analgesic drug in different models of inflammatory pain.Aim: This study aimed to evaluate the effects of systemically or locally injected tramadol with/without systemically injected magnesium sulfate in prophylactic or therapeutic protocols of application in a rat model of somatic inflammation.Methods: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0.1 ml, 0.5%). The antihyperalgesic/antiedematous effects of tramadol (intraperitoneally or intraplantarly injected), and tramadol-magnesium sulfate (subcutaneously injected) combinations were assessed by measuring the changes in paw withdrawal thresholds or paw volume induced by carrageenan. The drugs were administered before or after inflammation induction.Results: Systemically administered tramadol (1.25–10 mg/kg) before or after induction of inflammation reduced mechanical hyperalgesia and edema with a maximal antihyperalgesic/antiedematous effect of about 40–100%. Locally applied tramadol (0.125 mg/paw) better reduced edema (50–100%) than pain (20–50%) during 24 h. Administration of a fixed dose of tramadol (1.25 mg/kg) with different doses of magnesium led to a dose-dependent enhancement and prolongation of the analgesic effect of tramadol both in prevention and treatment of inflammatory pain. Magnesium increases the antiedematous effect of tramadol in the prevention of inflammatory edema while reducing it in treatment.Conclusion: According to results obtained in this animal model, systemic administration of low doses of tramadol and magnesium sulfate given in combination is a potent, effective and relatively safe therapeutic option for prevention and especially therapy of somatic inflammatory pain. The best result is achieved when tramadol is combined with magnesium sulfate at a dose that is equivalent to the average human recommended daily dose and when the drugs are administered when inflammation is maximally developed.

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P2X7‐induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C‐fibres sensitization

Teixeira

Pimentel

Abdalla

et al. 2021

European Journal of Pain

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Background: P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ. Methods: The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenate for enzyme-linked immunosorbent assay, leukocyte infiltration and western blotting analysis. Results: The nonselective P2X7 receptor agonist BzATP induced a dose-dependent TMJ nociception, which was blocked by the selective P2X7 receptor antagonist A-438079. The co-administration of the selective β2-adrenoceptor antagonist (ICI-118,551) and the pre-treatment with cyclooxygenase inhibitor indomethacin or with the nonspecific selectin inhibitor Fucoidan significantly reduced BzATP-induced TMJ nociception. BzATP also induced an increase of pro-inflammatory cytokines TNFα, IL-1β and CINC-1 levels, as well as leukocyte recruitment in TMJ tissue, effects that were reduced by A-438079. Moreover BzATP-induced TMJ nociception was inhibited in rats neonatal-treated with Capsaicin (depleting C-fibers). Finally, BzATP-induced an increase in TRPV1 expression in TMJ tissue. Conclusions: These findings suggest that P2X7 receptor activation in TMJ of rats induces nociceptive responses mediated by sympathomimetic amines, prostaglandins, leukocyte migration and increased levels of pro-inflammatory cytokines.Furthermore, the P2X7 receptor activation induces nociceptive responses dependent on the activation of the primary afferent nociceptors of rats' TMJ. Significance: The activation of P2X7 receptors has an essential role in TMJ nociception and could be an interesting target to control the inflammatory pain in temporomandibular disorders.How to cite this article: Teixeira JM, Pimentel RM, Abdalla HB, et al. P2X7-induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C-fibres sensitization.

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The anti-inflammatory effect of tramadol in the temporomandibular joint of rats

Cited by 25 publications

References 58 publications

Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception

Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

P2X7‐induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C‐fibres sensitization

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