Search

Introduction Pain-related behavior secondary to masticatory function can be assessed with the rodent bite force model. A reduction of the bite force has been shown to be related to pain associated with the masseter muscle and jaw activity, while an increase in bite force suggests improvement of muscle function and less pain. To evaluate the usefulness of the bite force measure in studying long-lasting orofacial pain we analyzed biting parameters during prolonged myofascial pain induced by ligation injury of the masseter muscle tendon (TL) in mice. Methods C57Bl/6 mice were habituated to bite at a pair of aluminum plates attached to a force displacement transducer. The transduced voltage signals were amplified and converted to force through calibration with a standard weight set. Voluntary biting behavior was recorded for 100 s/session and those with bite forces ≥980 mN were analyzed. Nociception was also verified with von Frey, conditioned place avoidance (CPA) tests and mouse grimace scale. Persistent orofacial pain was induced with unilateral ligation of one tendon of the masseter muscle (TL). Results To reduce interference of random bites of smaller forces, the top 5 or 15 bite forces (BF5/15) were chosen as a measure of masticatory function and related to pain behavior. Both male and female mice exhibited similar BF5/15. For the first nascent test of all mice, mean bite force was significantly and positively correlated with the body weight. However, this correlation was less clear in the latter tests (2–8 w). TL induced a reduction of BF5/15 that peaked at 1 w and returned to the baseline within 3 w. The von Frey and CPA tests indicated that mechanical allodynia/hyperalgesia persisted at the time when the BF had returned to the pre-injury level. Infusion of pain-relieving bone marrow stromal cells improved biting behavior in both male and female mice as shown by significantly increased BF5/15, compared to vehicle-treated mice. Conclusions Mouse voluntary biting behavior can be reliably measured and quantified with a simplified setup. The bite force showed an inverse relationship with the level of pain after TL and was improved by pain-relieving manipulations. However, the injury-induced reduction of bite force peaked early and did not parallel with other measures of nociception in the later phase of hyperalgesia. The results suggest that multiple factors such as the level of habituation, cognitive motive, physical status, and feeding drive may affect random voluntary biting and confound the biting parameters related to maintained hyperalgesia.

An environment-friendly methodology for the synthesis of 1,2,4-triazoline derivatives on water is described. This method provides an environmental and useful strategy for catalyst-free synthesis of 1,2,4-triazolines derivatives. The gram scale reaction and one-pot reaction are also performed to ensure the scalability and high efficiency of the reaction.

Oxytocin is a well-known neurohypophysial hormone that plays an important role in behavioral anxiety and nociception. Two major forms of long-term potentiation, presynaptic LTP (pre-LTP) and postsynaptic LTP (post-LTP), have been characterized in the anterior cingulate cortex (ACC). Both pre-LTP and post-LTP contribute to chronic-pain-related anxiety and behavioral sensitization. The roles of oxytocin in the ACC have not been studied. Here, we find that microinjections of oxytocin into the ACC attenuate nociceptive responses and anxiety-like behavioral responses in animals with neuropathic pain. Application of oxytocin selectively blocks the maintenance of pre-LTP but not post-LTP. In addition, oxytocin enhances inhibitory transmission and excites ACC interneurons. Similar results are obtained by using selective optical stimulation of oxytocin-containing projecting terminals in the ACC in animals with neuropathic pain. Our results demonstrate that oxytocin acts on central synapses and reduces chronic-pain-induced anxiety by reducing pre-LTP.

Dexmedetomidine, a selective alpha 2-adrenoceptor (α2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the α2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.