title: Role of sympathetic nervous system in rat model of chronic visceral pain.
abstract: BACKGROUND
  Changes in central pain modulation have been implicated in generalized pain syndromes such as irritable bowel syndrome (IBS). We have previously demonstrated that reduced descending inhibition unveils a role of sympathoneuronal outflow in decreasing peripheral sensory thresholds, resulting in stress-induced hyperalgesia. We investigated whether sympathetic nervous system (SNS) exacerbation of pain sensation when central pain inhibition is reduced is relevant to chronic pain disorders using a rat colon irritation (CI) model of chronic visceral hypersensitivity with hallmarks of IBS.
  
  
  METHODS
  Rats were treated to a series of colorectal balloon distensions (CRD) as neonates resulting in visceral and somatic hypersensitivity and altered stool function that persists into adulthood. The visceral sensitivity was assessed by recording electromyographic (EMG) responses to CRD. Somatic sensitivity was assessed by paw withdrawal thresholds to radiant heat. The effects on the hypersensitivity of (i) inhibiting sympathoneuronal outflow with pharmacological and surgical interventions and (ii) enhancing the outflow with water avoidance stress (WAS) were tested.
  
  
  RESULTS
  The alpha2-adrenergic agonist, clonidine, and the alpha1-adrenergic antagonist, prazosin, reduced the visceral hypersensitivity and WAS enhanced the pain. Chemical sympathectomy with guanethidine and surgical sympathectomy resulted in a loss of the chronic visceral hypersensitivity.
  
  
  CONCLUSIONS
  The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes.
authors.affiliation: Allergan, Irvine, CA, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Gil
authors.affiliation: University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gu
authors.affiliation: Allergan, Irvine, CA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Donello
authors.affiliation: Allergan, Irvine, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cabrera
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut (AUB), Beirut, Lebanon.|Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Al-Chaer
mesh_terms: D000818:Animals; D059350:Chronic Pain; D004195:Disease Models, Animal; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D059265:Visceral Pain / Q000503:physiopathology*
keywords: alpha-adrenergic receptors; animal model; behavior; chronic pain; irritable bowel syndrome; sympathetic nervous system; visceral pain