Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR⁺) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR⁺ neurons directly regulate the mPFC-NAcShell circuit via GABA_A receptors. Thus, the MOR⁺ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals ; Nucleus Accumbens/drug effects* ; Prefrontal Cortex/drug effects* ; Nicotine/pharmacology* ; Receptors, Opioid, mu/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Tobacco Use Disorder/metabolism* ; Neurons/drug effects* ; Neural Pathways/drug effects*

Background/Aims: Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation. Methods: The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. AfterYKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase(p-ERK) 1/2 in the spinal cord was performed. Results: YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord.In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility. Conclusions YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract.This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.

Recently, the palliative care team (PCT) at our hospital has included dentists. Among a total of 127 cancer patientsand required PCT intervention from 2009 to 2014, 17 patients (13.3%) had oral symptoms. Therefore, the PCT held discussions in order to determine the optimal way to treat each patient. Various symptoms, including oral pain, dry mouth, taste disturbance, furred tongue, excessive amounts of saliva, appetite loss, and trismus were treated by the dentists. As a result, the oral findings improved in all patients, while the oral symptoms improved in 16 of the 17 patients (94%). Thanks to the fact that dentists have joined the PCT, oral symptoms are effectively relieved, and PCT members now have an increased interest in oral cavity complications. Furthermore, conducting thorough examinations of the oral cavity by the PCT not only results in an improved QOL, but it has also increased the interest in the oral cavity on the part of the PCT. Therefore, more effective palliative care is expected to be achieved by promoting increased cooperation with more clinical departments.

[Objective]Capsaicin induces flare reaction in the human skin, and repetitive capsaicin applications induce capsaicin desensitization. To investigate the receptors related to flare reaction by acupuncture and moxibustion, we measured pain thresholds and flare reaction in two areas.
[Methods]Thirteen healthy volunteers with informed consent participated in this study. Capsaicin (0.1%) was applied repetitively (6 h/3days) to the forearm skin to desensitize the area. Then, mechanical and heat pain thresholds, flare reactions that induced by acupuncture and moxibustion were measured.
[Results]In the desensitized area, the heat pain threshold was significantly increased but the mechanical pain threshold did not change. Moxibustion induced flare reaction and it was significantly diminished under capsaicin desensitization. On the other hand, acupuncture induced flare reaction and it disappeared completely under capsaicin desensitization.
[Discussion and Conclusion]These results revealed that the flare reaction induced by acupuncture and moxibustion requires TRPV1 activation. For the moxibustion, flare reaction was significantly diminished under capsaicin desensitization but remained significant. Therefore we suggest that TRPV1 mainly mediates the flare reaction but other heat sensitive receptors might be involved in flare reaction. While the mechanical pain threshold was not changed under capsaicin desensitization, flare reaction induced by acupuncture disappeared completely. This suggests that flare reaction is not induced by the mechanical stimuli of acupuncture itself, but other factors such as inflammatory mediators released from damaged cell causing flare reaction by acupuncture.