• Peripheral mechanisms contribute to comorbid visceral hypersensitivity induced by preexisting orofacial pain and stress in female rats

      Ji, Y.; Hu, B.; Klontz, C.; Li, J.; Dessem, D.; Dorsey, S.G.; Traub, R.J. (Blackwell Publishing Ltd, 2020)
      Background: Stress exacerbates many chronic pain syndromes including irritable bowel syndrome (IBS). Among these patient populations, many suffer from comorbid or chronic overlapping pain conditions and are predominantly female. Nevertheless, basic studies investigating chronic psychological stress-induced changes in pain sensitivity have been mostly carried out in male rodents. Our laboratory developed a model of comorbid pain hypersensitivity (CPH) (stress in the presence of preexisting orofacial pain inducing chronic visceral pain hypersensitivity that significantly outlasts transient stress-induced pain hypersensitivity (SIH)) facilitating the study of pain associated with IBS. Since CPH and SIH are phenotypically similar until SIH resolves and CPH persists, it is unclear if underlying mechanisms are similar. Methods: In the present study, the visceromotor response (VMR) to colorectal distention was recorded in the SIH and CPH models in intact females and ovariectomized rats plus estradiol replacement (OVx + E2). Over several months, rats were determined to be susceptible or resilient to stress and the role of peripheral corticotrophin-releasing factor (CRF) underlying in the pain hypersensitivity was examined. Key Results: Stress alone induced transient (3-4 weeks) visceral hypersensitivity, though some rats were resilient. Comorbid conditions increased susceptibility to stress prolonging hypersensitivity beyond 13 weeks. Both models had robust peripheral components; hypersensitivity was attenuated by the CRF receptor antagonist astressin and the mast cell stabilizer disodium cromoglycate (DSCG). However, DSCG was less effective in the CPH model compared to the SIH model. Conclusions and Inferences: The data indicate many similarities but some differences in mechanisms contributing to comorbid pain conditions compared to transient stress-induced pain. Copyright 2020 The Authors.
    • The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System

      Tao, Z.-Y.; Wang, P.-X.; Traub, R.J. (Hindawi Limited, 2019)
      Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders but without structural or specific tissue pathologies. CPP is becoming a serious health problem in clinical practice due to the unknown cause of intractable pain and high cost of health care yet has not been satisfactorily addressed. During the past decades, a significant role for the descending pain modulation and alterations due to specific diseases of CPP has been emphasized. It has been widely established that central sensitization and alterations in neuroplasticity induced by the enhancement of descending pain facilitation and/or the impairment of descending pain inhibition can explain many chronic pain states including CPP. The descending serotonergic neurons in the raphe nuclei target receptors along the descending pain circuits and exert either pro- or antinociceptive effects in different pain conditions. In this review, we summarize the possible underlying descending pain regulation mechanisms in CPP and the role of serotonin, thus providing evidence for potential application of analgesic medications based on the serotonergic system in CPP patients. Copyright 2019 Zhuo-Ying Tao et al.