Blockade of peripheral 5HT3 receptor attenuates the formalin-induced nocifensive behavior in persistent temporomandibular joint inflammation of rat

Okamoto, Keiichiro; Imbe, Hiroki; Tashiro, Akimasa; Kumabe, Shunji; Senba, Emiko

doi:10.1016/j.neulet.2004.06.017

Cited by 41 publications

(13 citation statements)

References 26 publications

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“…*P , 0.05; **P , 0.01; ***P , 0.001 by Dunnett's test vs. vehicle-treated group. (Colpaert et al, 2002); intrathecally administered 5-HT 3 receptor antagonists reduced the second phase of formalininduced nociceptive behavior (Okamoto et al, 2004); and the 5-HT 3 antagonist ondansetron inhibited thermally and mechanically evoked neuronal responses of wide-dynamic-range neurons of rats 14 days after spinal nerve ligation (Suzuki et al, 2004). Although further investigation is needed, other mechanisms such as an agonistic action on 5-HT 1A receptors and an antagonistic action on 5-HT 3 receptors could contribute to the analgesic effects of AS1069562, with its different profile from currently used antidepressants.…”

Section: Discussionmentioning

confidence: 98%

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Murai

Aoki

Tamura

et al. 2013

J Pharmacol Exp Ther

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AS1069562 [(R)-2-[(1H-inden-7-yloxy)methyl]morpholine monobenzenesulfonate] is the (1)-isomer of indeloxazine, which had been used clinically for the treatment of cerebrovascular diseases with multiple pharmacological actions, including serotonin (5-HT) and norepinephrine (NE) reuptake inhibition. Here we investigated the analgesic effects of AS1069562 in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and the spinal monoamine turnover. These effects were compared with those of the antidepressants duloxetine and amitriptyline. AS1069562 significantly elevated extracellular 5-HT and NE levels in the rat spinal dorsal horn, although its 5-HT and NE reuptake inhibition was much weaker than that of duloxetine in vitro. In addition, AS1069562 increased the ratio of the contents of both 5-HT and NE to their metabolites in rat spinal cord, whereas duloxetine slightly increased only the ratio of the content of 5-HT to its metabolite. In CCI rats, AS1069562 and duloxetine significantly ameliorated mechanical allodynia, whereas amitriptyline did not. AS1069562 and amitriptyline significantly ameliorated thermal hyperalgesia, and duloxetine tended to ameliorate it. Furthermore, AS1069562, duloxetine, and amitriptyline significantly improved spontaneous pain-associated behavior. In a gastric emptying study, AS1069562 affected gastric emptying at the same dose that exerted analgesia in CCI rats. On the other hand, duloxetine and amitriptyline significantly reduced gastric emptying at lower doses than those that exerted analgesic effects. These results indicate that AS1069562 broadly improved various types of neuropathic pain-related behavior in CCI rats with unique characteristics in spinal monoamine turnover, suggesting that AS1069562 may have potential as a treatment option for patients with neuropathic pain, with a different profile from currently available antidepressants.

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Section: Discussionmentioning

confidence: 98%

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Murai

Aoki

Tamura

et al. 2013

J Pharmacol Exp Ther

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“…However, a number of studies suggest that activation of peripheral 5HT 3 receptors induces pro-nociceptive effects. Local administration of 5HT 3 receptor antagonists have been shown to be analgesic in acute and chronic pain[30], and in a model of persistent temporomandibular joint inflammation[31]. In humans, topical ondansetron attenuates the nociceptive and inflammatory effects of intradermal capsaicin[32].…”

Section: Discussionmentioning

confidence: 99%

Serotonin enhances urinary bladder nociceptive processing via a 5-HT3 receptor mechanism

Hall

DeWitte

Ness

et al. 2015

Neuroscience Letters

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Serotonin from the descending pain modulatory pathway is critical to nociceptive processing. Its effects on pain modulation may either be inhibitory or facilitatory, depending on the type of pain and which receptors are involved. Little is known about the role of serotonergic systems in bladder nociceptive processing. These studies examined the effect of systemic administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP), on normal bladder and somatic sensation in rats. ELISA was used to quantify peripheral and central changes in serotonin and its major metabolite following 5-HTP administration, and the potential role of the 5-HT3 receptor on changes in bladder sensation elicited by 5-HTP was investigated. 5-HTP produced bladder hypersensitivity and somatic analgesia. The pro-nociceptive effect of 5-HTP was attenuated by intrathecal, but not systemic, ondansetron. Peripheral increases in serotonin, its metabolism and rate of turnover were detectable within 30 min of 5-HTP administration. Significant enhancement of serotonin metabolism was observed centrally. These findings suggest that 5-HTP increases serotonin, which may then affect descending facilitatory systems to produce bladder hypersensitivity via activation of spinal 5-HT3 receptors.

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“…The RVM, and more specifically, 5HT3R-related mechanisms have been implicated in descending facilitation of nociception in several neuropathic (Wei et al, 2010, Okubo et al, 2013) and inflammatory pain models (Okamoto et al, 2004, Zhao et al, 2007). However, the relationship between the RVM, descending pain facilitatory pathways and psychophysical stress is less well defined.…”

Section: Discussionmentioning

confidence: 99%

“…The family of 5HT receptors consists of seven groups and 15 receptor subtypes (Viguier et al, 2013). The 5HT3 receptor (5HT3R) is the only ligand-gated 5HT receptor subtype and has been linked to pain facilitation in animal models for spinal (Suzuki et al, 2002, Zeitz et al, 2002, Rygh et al, 2006, Svensson et al, 2006) and craniofacial pain (Okamoto et al, 2004, Okamoto et al, 2005, Okubo et al, 2013, Kim et al, 2014). However, the role of 5HT3R in clinical pain management remains uncertain (Faerber et al 2007; Machu 2011).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats

et al. 2015

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Repeated forced swim (FS) conditioning enhances nociceptive responses to temporomandibular joint (TMJ) stimulation in male and female rats. The basis for FS-induced TMJ hyperalgesia remains unclear. To test the hypothesis that serotonin 3 receptor (5HT3R) mechanisms contribute to enhanced TMJ nociception after FS, ovariectomized female rats were treated with estradiol and subjected to FS for three days. On day 4, rats were anesthetized with isoflurane and TMJ-responsive neurons were recorded from superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical (Vc/C1–2) region and electromyographic (EMG) activity was recorded from the masseter muscle. Only Vc/C1–2 neurons activated by intra-TMJ injections of ATP were included for further analysis. Although neurons in both superficial and deep laminae were activated by ATP, only neurons in deep laminae displayed enhanced responses after FS. Local application of the 5HT3R antagonist, ondansetron (OND), at the Vc/C1–2 region reduced the ATP-evoked responses of neurons in superficial and deep laminae and reduced the EMG response in both sham and FS rats. OND also decreased the spontaneous firing rate of neurons in deep laminae and reduced the high threshold convergent cutaneous receptive field area of neurons in superficial and deep laminae in both sham and FS rats. These results revealed that central application of a 5HT3R antagonist, had widespread effects on the properties of TMJ-responsive neurons at the Vc/C1–2 region and on jaw muscle reflexes under sham and FS conditions. It is concluded that 5HT3R does not play a unique role in mediating stress-induced hyperalgesia related to TMJ nociception.

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Blockade of peripheral 5HT3 receptor attenuates the formalin-induced nocifensive behavior in persistent temporomandibular joint inflammation of rat

Cited by 41 publications

References 26 publications

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

AS1069562, the (+)-Isomer of Indeloxazine, Exerts Analgesic Effects in a Rat Model of Neuropathic Pain with Unique Characteristics in Spinal Monoamine Turnover

Serotonin enhances urinary bladder nociceptive processing via a 5-HT3 receptor mechanism

Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats

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