Tu2124 P2X7 Receptor Modulate Primary Afferent Responses to Colorectal Distension in Rat Models With Visceral Pain

2013 ◽  
Vol 144 (5) ◽  
pp. S-935-S-936
Author(s):  
Jing Wang ◽  
Elie D. Al-Chaer
Keyword(s):  
P2x7 Receptor ◽  
Visceral Pain ◽  
Colorectal Distension ◽  
Primary Afferent ◽  
Rat Models

T1836 Gabapentin Reverses Colorectal Distension-Induced Visceral Pain Behaviours in Rat Models of Acute and Chronic Visceral Hypersensitivity

2008 ◽  
Vol 134 (4) ◽  
pp. A-573
Author(s):  
Anne-Marie Coelho ◽  
Siobhain M. O'Mahony ◽  
Colleen M. Taylor ◽  
Alan Wheeldon ◽  
Patrick Fitzgerald ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Colorectal Distension ◽  
Rat Models

scholarly journals Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice

2010 ◽  
Vol 298 (1) ◽  
pp. G81-G91 ◽  
Author(s):  
Fiore Cattaruzza ◽  
Ian Spreadbury ◽  
Marcela Miranda-Morales ◽  
Eileen F. Grady ◽  
Stephen Vanner ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Visceral Pain ◽  
Receptor Potential ◽  
Afferent Neurons ◽  
Visceral Hyperalgesia ◽  
Spinal Neurons ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Transient Receptor

The excitatory ion channel transient receptor potential ankyrin-1 (TRPA1) is prominently expressed by primary afferent neurons and is a mediator of inflammatory pain. Inflammatory agents can directly activate [e.g., hydroxynonenal (HNE), prostaglandin metabolites] or indirectly sensitize [e.g., agonists of protease-activated receptor (PAR2)] TRPA1 to induce somatic pain and hyperalgesia. However, the contribution of TRPA1 to visceral pain is unknown. We investigated the role of TRPA1 in visceral hyperalgesia by measuring abdominal visceromotor responses (VMR) to colorectal distention (CRD) after intracolonic administration of TRPA1 agonists [mustard oil (MO), HNE], sensitizing agents [PAR2 activating peptide (PAR2-AP)], and the inflammatory agent trinitrobenzene sulfonic acid (TNBS) in trpa1+/+ and trpa1−/− mice. Sensory neurons innervating the colon, identified by retrograde tracing, coexpressed immunoreactive TRPA1, calcitonin gene-related peptide, and substance P, expressed TRPA1 mRNA and responded to MO with depolarizing currents. Intracolonic MO and HNE increased VMR to CRD and induced immunoreactive c-fos in spinal neurons in trpa1 +/+ but not in trpa1 −/− mice. Intracolonic PAR2-AP induced mechanical hyperalgesia in trpa1 +/+ but not in trpa1 −/− mice. TNBS-induced colitis increased in VMR to CRD and induced c-fos in spinal neurons in trpa1 +/+ but not in trpa1 −/− mice. Thus TRPA1 is expressed by colonic primary afferent neurons. Direct activation of TRPA1 causes visceral hyperalgesia, and TRPA1 mediates PAR2-induced hyperalgesia. TRPA1 deletion markedly reduces colitis-induced mechanical hyperalgesia in the colon. Our results suggest that TRPA1 has a major role in visceral nociception and may be a therapeutic target for colonic inflammatory pain.

Raphe Magnus Neurons Help Protect Reactions to Visceral Pain From Interruption by Cutaneous Pain

2006 ◽  
Vol 96 (6) ◽  
pp. 3423-3432 ◽  
Author(s):  
Thaddeus S. Brink ◽  
Kevin M. Hellman ◽  
Aaron M. Lambert ◽  
Peggy Mason
Keyword(s):  
Cellular Response ◽  
Receptor Agonist ◽  
Visceral Pain ◽  
Noxious Stimulus ◽  
Colorectal Distension ◽  
Cutaneous Stimulation ◽  
Cell Discharge ◽  
Raphe Magnus ◽  
Life Threatening ◽  
On And Off Cells

Suppression of reactions to one noxious stimulus by a spatially distant noxious stimulus is termed heterotopic antinociception. In lightly anesthetized rats, a noxious visceral stimulus, colorectal distension (CRD), suppressed motor withdrawals but not blood pressure or heart rate changes evoked by noxious hindpaw heat. Microinjection of muscimol, a GABAA receptor agonist, into raphe magnus (RM) reduced CRD-evoked suppression of withdrawals, evidence that RM neurons contribute to this heterotopic antinociception. To understand how brain stem neurons contribute to heterotopic antinociception, RM neurons were recorded during CRD-elicited suppression of hindpaw withdrawals. Although subsets of RM neurons that were excited (on cells) or inhibited (off cells) by noxious cutaneous stimulation were either excited or inhibited by CRD, on cells were inhibited and off cells excited by an intracerebroventricularly administered opioid, evidence that the nociception-facilitating and -inhibiting functions of on and off cells, respectively, are predicted by the cellular response to noxious cutaneous stimulation alone and not by the response to CRD. When recorded during CRD-elicited antinociception, RM cell discharge resembled the pattern observed in response to CRD stimulation alone. However, when hindpaw withdrawal suppression was incomplete, RM cell discharge resembled the pattern observed in response to heat alone. We propose that on cells excited by CRD facilitate responses to CRD itself, which in turn augments excitation of off cells that then act to suppress cutaneous nociception. RM cells may thereby contribute to the dominance of quiet recuperative reactions evoked by potentially life-threatening visceral stimuli over transient somatomotor activity elicited by less-injurious noxious cutaneous stimuli.

Assessment of Visceral Pain-Related Pseudo-Affective Responses to Colorectal Distension in Mice by Intracolonic Manometric Recordings

2006 ◽  
Vol 7 (2) ◽  
pp. 108-118 ◽  
Author(s):  
Susanne Arvidsson ◽  
Marie Larsson ◽  
Håkan Larsson ◽  
Erik Lindström ◽  
Vincente Martinez
Keyword(s):  
Visceral Pain ◽  
Affective Responses ◽  
Colorectal Distension

Calcitonin gene-related peptide in viscerosensitive response to colorectal distension in rats

1997 ◽  
Vol 273 (1) ◽  
pp. G191-G196 ◽  
Author(s):  
V. Plourde ◽  
S. St-Pierre ◽  
R. Quirion
Keyword(s):  
Acetic Acid ◽  
Visceral Pain ◽  
Intrathecal Administration ◽  
Calcitonin Gene Related Peptide ◽  
Visceral Hyperalgesia ◽  
Afferent Pathways ◽  
Colorectal Distension ◽  
Related Peptide ◽  
Balloon Distension ◽  
Calcitonin Gene

The role of calcitonin gene-related peptide (CGRP) on colorectal distension-induced visceral pain was investigated in conscious rats. Intracolonic administration of acetic acid (0.6%) resulted in a significantly increased number of abdominal contractions in response to colorectal balloon distension from 5.8 +/- 1.2 in controls to 16.6 +/- 1.0 in acetic acid-treated animals (P < 0.05), evidencing sensitization of visceral afferent pathways and subsequently visceral hyperalgesia. This sensitization phenomenon was not observed in animals previously treated with systemic capsaicin. Likewise, in animals not treated with capsaicin, use of an intravenous antagonist for CGRP [human CGRP-(8-37)], completely reversed the sensitizing effects of acetic acid. Furthermore, intravenous administration of CGRP dose dependently increased the number of abdominal contractions in response to colorectal distension from 3.0 +/- 1.1 (CGRP 250 ng) to 17.0 +/- 1.2 (CGRP 500 ng, P < 0.05), as previously observed in acetic acid-treated animals. Finally, intrathecal administration of hCGRP-(8–37) (mid-lumbar) also resulted in a total dose-dependent reversal of CGRP (500 ng) or acetic acid-induced visceral hypersensitivity. These results demonstrate that CGRP plays a major role in this model of visceral afferent nerve sensitization from gastrointestinal origin.

scholarly journals Glomerular expression of the ATP-sensitive P2X7 receptor in diabetic and hypertensive rat models

2004 ◽  
Vol 66 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Oliver Vonend ◽  
Clare M. Turner ◽  
Choong M. Chan ◽  
Andrew Loesch ◽  
G. Carmen Dell'Anna ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Rat Models ◽  
Hypertensive Rat

scholarly journals A reassessment of P2X7 receptor inhibition as a neuroprotective strategy in rat models of contusion injury

2012 ◽  
Vol 233 (2) ◽  
pp. 687-692 ◽  
Author(s):  
Alexander Marcillo ◽  
Beata Frydel ◽  
Helen M. Bramlett ◽  
W. Dalton Dietrich
Keyword(s):  
P2x7 Receptor ◽  
Rat Models ◽  
Receptor Inhibition ◽  
Neuroprotective Strategy ◽  
Contusion Injury

Central mechanisms of visceral pain

1991 ◽  
Vol 69 (5) ◽  
pp. 627-634 ◽  
Author(s):  
G. F. Gebhart ◽  
T. J. Ness
Keyword(s):  
Connective Tissue ◽  
Constant Pressure ◽  
Visceral Pain ◽  
Present Report ◽  
Clinical Importance ◽  
Pain Modulation ◽  
Colorectal Distension ◽  
Pain Model ◽  
Autonomic Responses ◽  
Colon And Rectum

Deep pain arising from muscle, joints, connective tissue, and the viscera is different in character and quality from pain arising from cutaneous structures. Deep pains, particularly visceral pain, are poorly localized, typically referred or transferred to a cutaneous site, and generally produce strong emotional and autonomic responses and tonic muscle contractions. Despite the prevalence and clinical importance of deep pains, it is only relatively recently that investigative efforts have begun to focus on the mechanisms of deep pain. The present report briefly reviews the development and use of a model of visceral pain that employs constant pressure distension of the colon and rectum as a noxious stimulus. Converging behavioral, pharmacological, and physiological evidence that colorectal distension is a valid, reliable, noxious, visceral stimulus is presented.Key words: visceral pain, colorectal distension, pain modulation, pain model, adequate visceral stimuli.

scholarly journals Estrogen re-enhanced prenatal stress-related visceral sensitization and pain regulation

2020 ◽  
Author(s):  
Jinghong Chen ◽  
Ying Sun ◽  
Jinbao Wei ◽  
Peijun Ju ◽  
Qinjie Li ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Prenatal Stress ◽  
Pain Sensitivity ◽  
Visceral Pain ◽  
Afferent Fiber ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Primary Afferent

Abstract Background: Visceral pain is one of the most common sign of irritable bowel syndrome (IBS). Chronic stress during pregnancy may increase visceral pain sensitivity of offspring in a sexdependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen exacerbates visceral hypersensitivity in female rodents in pre-clinical models, we predicted that chronic prenatal stress (CPS) plus chronic adult stress (CAS) will maximize visceral pain sensitivity; and estrogen plays an important role in this hyperalgesia.Methods: The CPS plus CAS rodent model was established in which the balloon was used to distend colorectum. Meanwhile, the single fiber recording in vivo and patch-clamp experiments in vitro were used to monitor neuronal activity. The RT-PCR, Western Blot, and Immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity and molecular or transmission changes. We use Ovariectomy and Letrozole to treate female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization. Letrozole mainly used to reduce estrogen levels.Results: As predicted, CPS significantly increased single unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. And the activity in offspring females was significantly greater than the males. Besides, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increases in CPS + CAS rats that was associated with a decrease in transient A-type K+ current. Letrozole treatment decreases the colon DRG neuron excitability in females by decreasing the estrogen levels. Conclusions: This study adds to the growing evidence for the development of chronic stress induced visceral hypersensitivity in female, which involves estrogen-dependent sensitization of primary afferent colon neurons. Understanding this neurophysiological mechanisms will spur the development of female pain specific therapies.

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