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

Abstract

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.

Modulatory effects of repeated psychophysical stress on masseter muscle nociception in the nucleus raphe magnus of rats

“…Nociceptive transmission can be affected by psychophysical stress conditions, which can influence neural functioning with regard to pain circuits in the brain [2,3]. Prior studies have found that repeated forced swim tests (FSTs), which can induce psychophysical stress conditions, enhanced nociceptive neural excitabilities in the trigeminal subnucleus caudalis (Vc) region [4][5][6], with the Vc region being well documented as a critical area for mediating nociception in deep orofacial tissues, such as masseter muscle (MM) [7,8] and temporomandibular joints [4].…”

Blockade of 5‐HT3 receptors with granisetron does not affect trigeminothalamic nociceptive transmission in rats: Implication for migraine

“…It is worthy of note that the above‐mentioned efficacy of 5‐HT3 receptor antagonists in various models of trigeminal nociception (see Section ) has been demonstrated mostly under conditions of sustained sensitisation of different genesis, ie under persistent state of hyperalgesia which has been successfully eliminated by setrons . However, inactivation of 5‐HT3 receptors appeared to have low efficacy in acute pain conditions .…”

“…34,35 It is worthy of note that the above-mentioned efficacy of 5-HT3 receptor antagonists in various models of trigeminal nociception (see Section 1) has been demonstrated mostly under conditions of sustained sensitisation of different genesis, ie under persistent state of hyperalgesia which has been successfully eliminated by setrons. 12,13 However, inactivation of 5-HT3 receptors appeared to have low efficacy in acute pain conditions. 9,15 Furthermore, it has been shown that 5-HT3 receptor antagonists did not substantially alter the electrically evoked responses of dorsal horn neurons, 9,36 which coincides with the results of the presented study.…”

“…For example, there are clinical data demonstrating that setrons exert analgesic effect on both extracranial pain syndromes and various orofacial pain . Setrons have been reported to display analgesic, anti‐allodynic and anti‐hyperalgesic activities in animal models not only of non‐trigeminal, but also of trigeminal nociception . The latter is of particular interest since the trigeminal nerve, being functionally integrated together with the cranial blood vessels into the trigeminovascular system, plays a pivotal role in the pathogenesis of every cephalalgia .…”

“…7,8 Setrons have been reported to display analgesic, anti-allodynic and anti-hyperalgesic activities in animal models not only of non-trigeminal, 9,10 but also of trigeminal nociception. [11][12][13] The latter is of particular interest since the trigeminal Summary One way to expand the existing range of anti-migraine drugs seems to be the search for pharmacological agents with anti-cephalalgic properties among medicines approved for clinical indications other than migraine. Numerous experimental and clinical data imply that selective serotonin 5-HT3 receptor antagonists can be considered as potential antimigraine agents.…”