Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats

Itomi, Yasuo; Tsukimi, Yasuhiro; Kawamura, T.

doi:10.1016/j.ejphar.2016.05.011

Cited by 21 publications

(13 citation statements)

References 59 publications

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“…DNIC exerts also a differential control over Aβ -fibers, and Aδand C-fibers [33]. In this study, despite the fact that Aβ -fibers were probably more activated at HNS sites due to the use of a noxious clamp than at the test site where the sural nerve was electrically stimulated, the N-wave was reduced at 40 • C, suggesting a weakening of DNIC inhibition.…”

Section: Descending Pain Modulation Levelmentioning

confidence: 48%

Thermo-dependence of noxious mechanical heterotopic stimulation-dependent modulation of the spinal dorsal horn response to somatosensory stimulation

2018

J. Integr. Neurosci.

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Despite frequent clinical hyper-or hypothermia cases, the thermal-dependence of the endogenous pain modulation system at the spinal cord is not well understood. The spinal dorsal horn neuronal network responses during mechanical heterotopic noxious stimuli was evaluated at three different body temperatures (34, 37 or 40 • C) by measurement of lumbar cord dorsum potentials activated by electrical stimulation of the ipsilateral sural nerve in adult thiopental anesthetized rats. A noxious clamp was applied randomly to the tail, right hind paw, right forepaw, muzzle, or left forepaw. Heterotopic noxious stimuli induced a decrease of the negative wave amplitude and duration at 37 • C. This effect was reduced at 40 • C for both amplitude (−18.2% for 37-40 • C; p < 0.0005) and duration (−16.4% for 37-40 • C; p < 0.0001). The P wave showed neither amplitude nor duration changes at either of the three tested temperatures. Clinical range changes of temperature could modify pain sensation, while hyperthermia increased nociceptive sensory input to dorsal horn and exacerbated pain sensation in individuals with fever.

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Section: Descending Pain Modulation Levelmentioning

confidence: 48%

Thermo-dependence of noxious mechanical heterotopic stimulation-dependent modulation of the spinal dorsal horn response to somatosensory stimulation

2018

J. Integr. Neurosci.

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“…Specific alteration of rhythm in temperature (SART) stress which was an intermittent cold stress was applied for 5 days as a chronic stress model. This chronic stress model is reported to induce chronic visceral hypersensitivity and be useful as an IBS and fibromyalgia models . No body weight loss was observed during the stress period although an attenuation of weight gain was observed (data not shown).…”

Section: Resultsmentioning

confidence: 90%

“…In addition to the acute visceral pain model induced by restraint stress, we also evaluated the compound in the chronic visceral pain model induced by SART stress because it is important to investigate the efficacy in chronic model for development of drugs to treat IBS. This chronic stress model was established by repeating exposure to cold stress for 5 days and reported to be useful as a IBS and fibromyalgia models . Similar to IBS, fibromyalgia is also thought to be associated with stress and often coexists and overlaps with IBS .…”

Section: Discussionmentioning

confidence: 99%

“…SART stress was applied as described in the previous reports . Four‐week‐old male SD rats were kept in the grouped house (4 rats per cage) and were exposed to alternating one‐hour periods of cold (0°C) and room temperature (24°C) from 9:30 h‐16:30 h by repeated transfer into and out of a thermocontrolled incubator (MIR‐554, SANYO, Osaka, Japan), followed by sustained cold from 16:30 h‐9:30 h. This cycle was repeated four days to establish the SART stress model.…”

Section: Methodsmentioning

confidence: 99%

“…Single oral treatment of T‐3047928 at 3 and 10 mg/kg or alosetron at 3 and 10 mg/kg was carried out two or one hours prior to CRD. The dose of alosetron was selected based on the previous report by Itomi et al…”

Section: Methodsmentioning

confidence: 99%

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Pharmacological evaluation of a novel corticotropin‐releasing factor 1 receptor antagonist T‐3047928 in stress‐induced animal models in a comparison with alosetron

Itomi

Tanaka

Matsushita

et al. 2020

Neurogastroenterology Motil

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Background:The major symptoms of irritable bowel syndrome (IBS) are changes in bowel habits and abdominal pain. Psychological stress is the major pathophysiological components of IBS. Corticotropin-releasing factor (CRF) is a well-known integrator in response to psychological stress. In this study, a novel CRF1 receptor antagonist T-3047928 was evaluated in stress-induced IBS models of rats to explore its potency for IBS. Methods: Plasma adrenocorticotropic hormone (ACTH) levels after intravenous oCRH challenge were measured as a pharmacodynamic marker. Efficacies of oral T-3047928 were compared with oral alosetron, a 5-HT3 antagonist, on conditioning fear stress (CFS)-induced defecation, restraint stress (RS)-induced acute visceral pain, specific alteration of rhythm in temperature (SART) stress-induced chronic visceral pain, and normal defecation. Results: T-3047928 (1-10 mg/kg, p.o.) demonstrated a dose-dependent inhibition on oCRH-induced ACTH secretion. In disease models, T-3047928 suppressed fecal pellet output induced by CFS and improved both acute and chronic visceral hypersensitivity induced by RS and SART stress, respectively. Alosetron was also efficacious in stress-induced defecation and visceral pain models at 1 and 10 mg/kg, respectively.Alosetron, however, also suppressed normal defecation at lower those. On the other hand, T-3047928 did not change normal defecation even at higher dose than those in disease models. Conclusion:T-3047928 is an orally active CRF1 antagonist that demonstrated potent inhibitory effects in stress-associated IBS models with no effect on normal defecation. Therefore, it is suggested that T-3047928 may have a potency as a novel option for IBS-D therapy with minimal constipation risk. K E Y W O R D SAlosetron, CRF1 receptor antagonist, defecation, irritable bowel syndrome (IBS), stress, T-3047928, visceral pain

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Neuromodulation Through Magnetic Fields Irradiation with AT-04 Improves Hyperalgesia in a Rat Model of Neuropathic Pain via Descending Pain Modulatory Systems and Opioid Analgesia

Kohno,

Takaki,

Kishita

et al. 2023

Cell Mol Neurobiol

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Neuromodulation through magnetic fields irradiation with ait® (AT-04), a device that irradiates a mixed alternating magnetic fields (2 kHz and 83.3 MHz), has been shown to have high efficacy for fibromyalgia and low back pain in our previous clinical trials. The aim of this study was to elucidate the underlying analgesic mechanism of the AT-04 using the partial sciatic nerve ligation (PSL) model as an animal model of neuropathic pain. AT-04 was applied to PSL model rats with hyperalgesia and its pain-improving effect was verified by examining mechanical allodynia using the von Frey method. The results demonstrated a significant improvement in hyperalgesia in PSL model rats. We also examined the involvement of descending pain modulatory systems in the analgesic effects of AT-04 using antagonism by serotonin and noradrenergic receptor antagonists. These antagonists significantly reduced the analgesic effect of AT-04 on pain in PSL model rats by approximately 50%. We also measured the amount of serotonin and noradrenaline in the spinal fluid of PSL model rats using microdialysis during AT-04 treatment. Both monoamines were significantly increased by magnetic fields irradiation with AT-04. Furthermore, we evaluated the involvement of opioid analgesia in the analgesic effects of AT-04 using naloxone, the main antagonist of the opioid receptor, and found that it significantly antagonized the effects by approximately 60%. Therefore, the analgesic effects of AT-04 in PSL model rats involve both the endogenous pain modulation systems, including the descending pain modulatory system and the opioid analgesic system. Graphical Abstract

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Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats

Cited by 21 publications

References 59 publications

Thermo-dependence of noxious mechanical heterotopic stimulation-dependent modulation of the spinal dorsal horn response to somatosensory stimulation

Thermo-dependence of noxious mechanical heterotopic stimulation-dependent modulation of the spinal dorsal horn response to somatosensory stimulation

Pharmacological evaluation of a novel corticotropin‐releasing factor 1 receptor antagonist T‐3047928 in stress‐induced animal models in a comparison with alosetron

Neuromodulation Through Magnetic Fields Irradiation with AT-04 Improves Hyperalgesia in a Rat Model of Neuropathic Pain via Descending Pain Modulatory Systems and Opioid Analgesia

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