Chronic Visceral Hyperalgesia Research Articles

Herb-partition moxibustion relieves chronic visceral hyperalgesia and 5-HT concentration in colon mucosa of rats

Objective: The aim of this study was to evaluate the effect of herb-partition moxibustion on rectal sensory thresholds and to analyse possible mechanism of herb-partition moxibustion in treating chronic visceral hypersensitivity rats.Methods: Herb-partition moxibustion was administered to chronic visceral hypersensitivity rats for 7 days (once daily). Two moxa cylinders were used for each point in one treatment. Chronic visceral hypersensitivity rats without herb-partition moxibustion and normal rats were chosen as the control groups. Detection of abdominal withdrawal reflex was performed during 30–90 minutes after the first treatment. After seven treatments, a segment of distal colon (5 cm in length) was harvested, and 5-hydroxytryptamine concentration in the colon tissue was detected by enzyme-linked immunosorbent assay.Results: Herb-partition moxibustion significantly depressed abnormally increased AWR scores from the rectus abdominis in response to colorectal distention stimulation at strengths of 40 and 60 mmHg. Herb-partition moxibustion decreased 5-hydroxytryptamine concentration in colon tissue of chronic visceral hypersensitivity rats.Conclusion: Herb-partition moxibustion enhances the pain threshold of chronic visceral hypersensitivity rats and restores normal sensitivity by 5-hydroxytryptamine concentration decreased in the colon tissue. However, whether herb-partition moxibustion could enhance the pain threshold of IBS patients or not is not concluded in this study because of only small sample rats experiment.

Visceral afferents: What role in post-inflammatory pain?

Several weeks to several months after a bout of inflammation or an infectious event in a visceral organ, while inflammation or infection has resolved, defective nociceptive functions are sometimes still present, characterized by chronic pain symptoms, visceral hyperalgesia and allodynia. Visceral afferents which convey nociceptive messages have been shown to be hyperexcitable in inflammatory states. Only recently, studies have addressed visceral afferent electrical properties and neuroplastic changes in post-inflammatory situations. This review tries to appraise in post-inflammatory hypersensitive states, the most recent advances in the knowledge of visceral afferent inputs, together with in vivo recordings of visceral hyperalgesia and allodynia.

The Endogenous Hydrogen Sulfide Producing Enzyme Cystathionine-β Synthase Contributes to Visceral Hypersensitivity in a Rat Model of Irritable Bowel Syndrome

BackgroundThe pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH). CVH was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall.ResultsIn rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation.ConclusionOur results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

Suspended moxibustion relieves chronic visceral hyperalgesia via serotonin pathway in the colon

Experiments in rats have shown that chronic visceral hyperalgesia can be relieved by electro-acupuncture, but the efficacy of suspended moxibustion for relieving chronic visceral hyperalgesia is still unclear. The present study aimed to evaluate the effect of suspended moxibustion on rectal sensory thresholds and to analyze its possible mechanisms when treating chronic visceral hypersensitivity rats. Suspended moxibustion was administered once daily to 37-day-old chronic visceral hypersensitivity rats for 7 days. The two acupoints (ST25, bilateral) were simultaneously given suspended moxibustion. Each treatment lasted for 15 min. Rats in treatment of suspended moxibustion was not anesthetized. Untreated chronic visceral hypersensitivity rats and normal rats were used as controls. The abdominal withdrawal reflex was determined during 30–90 min after the first treatment. A 5-cm long segment of distal colon was harvested after seven treatments and 5-hydroxytryptamine concentrations in the colon were assayed by enzyme-linked immunosorbent assay. Abdominal withdrawal reflex scores from the rectus abdominis in response to colorectal distention were increased in rats with chronic visceral hypersensitivity, and the stimulation at strength of 20 mmHg was significantly depressed by suspended moxibustion. Suspended moxibustion increased the pain threshold and restored normal sensitivity by reducing 5-hydroxytryptamine concentrations in the colon of chronic visceral hypersensitivity rats.

Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats

Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V(3)) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V(3) signaling system in the development of stress-induced visceral hyperalgesia in rats. Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10-60 mmHg) was assessed before and after stress. Animals were treated daily with SSR149415 (0.3, 1, or 3 mg/kg ip 30 min before each WAS or sham WAS session), with a single dose of SSR149415 (1 mg/kg ip), or the selective corticotropin-releasing factor 1 (CRF(1)) antagonist DMP-696 (30 mg/kg po) before CRD at day 11. Effects of a single dose of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension. These data support a major role for V(3) receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V(3) pathway might represent an attractive alternative to the CRF/CRF(1) pathway for the treatment of chronic stress-related gastrointestinal disorders.

Visceral analgesics: drugs with a great potential in functional disorders?☆

Irritable bowel syndrome remains an incompletely understood, common syndrome with significant unmet medical needs. In IBS patients, abdominal pain is a primary factor related to quality of life impairment, symptom severity and health care utilization, and chronic visceral hyperalgesia has been identified as an important aspect of IBS pathophysiology. However, the development of therapies aimed at reducing this hyperalgesia (visceral analgesics) has been only partially successful despite preclinical evidence supporting the potential usefulness of several preclinical compounds aimed at peripheral as well as central targets.

A Rat Model of Chronic Postinflammatory Visceral Pain Induced by Deoxycholic Acid

Chronic visceral hyperalgesia is considered an important pathophysiologic symptom in irritable bowel syndrome (IBS); previous gastrointestinal inflammation is a potent etiologic factor for developing IBS. Although there are several animal models of adult visceral hypersensitivity after neonatal perturbation or acute colonic irritation/inflammation, current models of postinflammatory chronic visceral hyperalgesia are unsatisfactory. The aim of this study was to establish a model of chronic visceral hyperalgesia after colonic inflammation in the rat. Deoxycholic acid (DCA) was instilled into the rat colon daily for 3 days and animals were tested for up to 4 weeks. DCA induced mild, transient colonic inflammation within 3 days that resolved within 3 weeks. An exaggerated visceromotor response, referred pain to mechanical stimulation, increased spinal Fos expression, and colonic afferent and dorsal horn neuron activity were apparent by 1 week and persisted for at least 4 weeks, indicating chronic dorsal horn hyperexcitability and visceral hyperalgesia. There was no spontaneous pain, based on open field behavior. There was a significant increase in opioid-receptor activity. DCA induces mild, transient colitis, resulting in persistent visceral hyperalgesia and referred pain in rats, modeling some aspects of postinflammatory IBS.

P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity

Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by abdominal pain and bloating in association with altered bowel movements. Its pathogenesis and the underlying molecular mechanisms of visceral...

Expression of P2X Receptor in a Rat Model of Chronic Visceral Hyperalgesia

Expression of P2X Receptor in a Rat Model of Chronic Visceral Hyperalgesia

Neonatal gastric suctioning results in chronic visceral and somatic hyperalgesia: role of corticotropin releasing factor

Abstract Gastric suctioning is common in neonatal intensive care units. Studies suggest that gastric suctioning in premature infants may play a role in the development of visceral hyperalgesia. We hypothesized that repeated orogastric suctioning during the neonatal period results in chronic alterations in visceral and somatic sensation through a corticotropin-releasing factor mediated mechanism. Neonatal male Long Evans rats (n = 13) received daily orogastric suctioning for 10 days starting at postnatal day two (P2). Control rats (n = 15) were handled similarly without orogastric suction. A second study group was subjected to a similar protocol, only with pre-emptive administration of a CRF1 receptor antagonist (antalarmin, 20 mg/kg, IP) (n = 8). The control group received vehicle only (n = 8). An additional group was given antalarmin without suctioning (n = 5). After these rats grew to adulthood (PN 60), a visceromotor response to graded colorectal distension was recorded (10-80 mmHg, 30s, 180s inter-stimulus intervals) to assess changes in visceral sensitivity. Paw withdrawal latency to noxious heat applied to the hind paws was measured to assess changes in cutaneous sensitivity. Orogastric suctioning during the neonatal period results in global chronic somatic and visceral hyperalgesia in adult rats. Visceral hyperalgesia is prevented by pre-emptive administration of the CRF1 receptor antagonist, antalarmin.

Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensation

The role ofintramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague-Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10-80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13-L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions > or = 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 +/- 2.2 impulses s(-1)), but not SL-A neurons (5.3 +/- 0.9 impulses s(-1)) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 +/- 0.8 impulses s(-1); SL-A, 3.1 +/- 0.7 impulses s(-1)). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures > or = 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation.

Electro-acupuncture relieves chronic visceral hyperalgesia in rats

Acupuncture treatment is one of the most desirable choices for the management of pain including chronic visceral pain, but its scientific evidence and laws of action are not very clear at this point. In this study, we examined the immediate and cumulative effects of electro-acupuncture (EA) on chronic visceral pain induced by colorectal distention (CRD) stimuli in rats using an irritable bowel syndrome (IBS) model (a chronic visceral hypersensitivity model). The results demonstrated that EA could significantly depress both abnormally increased abdominal withdrawal reflex (AWR) scores and the magnitude of electromyograms (EMGs) recorded from the rectus abdominis in response to CRD stimulation at strengths of 20, 40, 60, and 80 mmHg. Repeated EA treatment for 14 days showed that the effects of EA on both abnormal AWRs and EMGs appeared 2–4 days after the start of the EA application session, gradually enhanced to its maximum within 8–12 days, and lasted 5 days after EA treatment stopped. These data provide evidence that visceral pain associated with the rat IBS model can be effectively treated by EA and opens up the possibility of clinical treatment of chronic visceral pain with acupuncture.

Sensitization in visceral pain and hyperalgesia

Humans experience both visceral pain and visceral hyperalgesia. Animal and clinical studies have documented differences in the anatomy and physiology of visceral sensory circuits as compared with somatic sensory pathways, providing mechanisms to explain some of the unique characteristics of visceral pain. Evidence further suggests that both peripheral and central sensitization increase visceral sensitivity, leading to the increased perception of pain—visceral hyperalgesia. A more thorough understanding of the mechanisms that underlie the processing of visceral stimuli will improve our ability to treat individuals suffering from acute and chronic visceral pain and hyperalgesia.