Physiology of Visceral Pain

Gebhart, G. F.; Bielefeldt, Klaus

doi:10.1002/cphy.c150049

Cited by 174 publications

(151 citation statements)

References 241 publications

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“…Visceral sensory neurons have many properties that differ from somatic sensory neurons and that are relevant to their distinct responses to analgesics, responses to injury and other pathophysiological perturbations (Robinson and Gebhart, 2008;Schwartz and Gebhart, 2014;Gebhart and Bielefeldt, 2016;Grundy et al, 2019). Our analyses of aggregated pelvic visceral sensory neurons provide the opportunity to understand the molecular contributors to these distinctive features that are shared by this population.…”

Section: Discussionmentioning

confidence: 99%

“…These conditions do not respond reliably to analgesics that are commonly administered for somatic pain, indicating that distinct mechanisms underlie their pathobiology. Healthy visceral sensory neurons also have distinct functional properties that underlie encoding of a wide range of changes within organs (Robinson and Gebhart, 2008;Sikandar and Dickenson, 2012;Schwartz and Gebhart, 2014;Gebhart and Bielefeldt, 2016). We are unaware of many of these internal changes, contrasting with our conscious awareness of somatic sensations such as heat, cold, touch, and vibration.…”

Section: Introductionmentioning

confidence: 99%

“…In rodents, the majority are located in dorsal root ganglia (DRG) in spinal levels lumbar 6 and sacral 1 (L6-S1; Dang et al, 2005;Xu and Gebhart, 2008;Forrest et al, 2013); we refer to these as "sacral" DRG as they are functionally equivalent to neurons found exclusively in sacral levels in humans. Pelvic visceral sensory neurons comprise two major classes, those with lightly myelinated (A-d ) or unmyelinated (C) axons (Dang et al, 2005;Franken et al, 2014;de Groat et al, 2015;Gebhart and Bielefeldt, 2016;Brierley et al, 2018). Many express transient receptor potential (TRP) channels that transduce noxious stimuli, including Trpv1, Trpa1, and Trpm8 (Skryma et al, 2011;Franken et al, 2014;Merrill et al, 2016), which are also expressed in subpopulations of somatic nociceptors (Patapoutian et al, 2009;Julius, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially leading to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively of somatic sensory neurons. This was performed in adult and E18.5 male and female mice. By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal levels. We identified many novel genes that had not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.In this study of mouse dorsal root ganglia (DRG), we have identified numerous features of sensory neurons that vary between lumbar and sacral spinal levels and that are potentially involved in unique physiology and pathophysiology of visceral sensation and pain. We further identify maturational components of this sacral visceral transcriptome by comparing data from embryonic and adult mice. There are limited sex differences across the transcriptome of embryonic or adult sensory ganglia, but in adults these can be revealed in sacral levels and especially in Trpv1 nociceptive neurons. These datasets will encourage identification of new tools to modify mature or developing sensory neurons and adult nociceptive pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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“…In visceral organs, sensory stimuli that reach noxious (painful) levels are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG) (Gebhart, ; Gebhart & Bielefeldt, ; Kyloh, Nicholas, Zagorodnyuk, Brookes, & Spencer, ; Spencer, Kyloh, Beckett, Brookes, & Hibberd, ). Spinal afferents are not only of supreme importance to our understanding of visceral nociception, but these neurons also play a major role in detecting innocuous stimuli that underlie local neural reflexes that do not reach conscious sensation.…”

Section: Introductionmentioning

confidence: 99%

Identifying unique subtypes of spinal afferent nerve endings within the urinary bladder of mice

Spencer

Greenheigh

Kyloh

et al. 2017

J of Comparative Neurology

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Spinal afferent neurons are responsible for the transduction and transmission of noxious (painful) stimuli and innocuous stimuli that do not reach conscious sensations from visceral organs to the central nervous system. Although the location of the nerve cell bodies of spinal afferents is well known to reside in dorsal root ganglia (DRG), the morphology and location of peripheral nerve endings of spinal afferents that transduce sensory stimuli into action potentials is poorly understood. The individual nerve endings of spinal afferents that innervate the urinary bladder have never been unequivocally identified in any species. We used an anterograde tracing technique developed in our laboratory to selectively label only spinal afferents. Mice were anesthetized and unilateral injections of dextran-amine made into lumbosacral DRGs (L5-S2). Seven to nine days postsurgery, mice were euthanized, the urinary bladder removed, then fresh-fixed and stained for immunoreactivity to calcitonin-gene-related-peptide (CGRP). Four distinct morphological types of spinal afferent ending in the bladder were identified. Three types existed in the detrusor muscle and one major type in the sub-urothelium and urothelium. Most nerve endings were located in detrusor muscle where the three types could be identified as having: "branching", "simple", or "complex" morphology. The majority of spinal afferent nerve endings were CGRP-immunoreactive. Single spinal afferent axons bifurcated many times upon entering the bladder and developed varicosities along their axon terminal endings. We present the first morphological identification of spinal afferent nerve endings in the mammalian urinary bladder.

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“…Visceral pain is difficult to manage effectively, largely because the visceral sensory mechanisms and factors that contribute to the pathogenesis of visceral pain are poorly understood [18]. Visceral hyperalgesia and central sensitization have been suggested to be part of the pathophysiology [19].…”

Section: Postoperative Painmentioning

confidence: 99%

Efficacy of ultrasound-guided rectus sheath block, butorphanol for single-incision laparoscopic cholecystectomy: A prospective, randomized, clinical trial

Zhong

Gao

et al. 2019

Preprint

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Background: Whether rectus sheath block (RSB) combined with butorphanol can relieve incisional pain and visceral pain in patients undergoing single-incision laparoscopic cholecystectomy (SILC) remains unknown. The goal of this study was to assess the efficacy of ultrasound-guided bilateral RSB, and butorphanol for postoperative analgesia in patients undergoing SILC.Methods: All 116 patients who met the criteria were randomly divided into four groups: group I, (n=29) general anaesthesia combined with patient-controlled intravenous analgesia (PCIA) (sufentanil 1 µg/ml); group II, (n=29) general anaesthesia combined with PCIA (butorphanol 0. 08 µg/ml); group III, (n=29) ultrasound-guided RSB (ropivacaine 100 mg) combined with PCIA (sufentanil 1 µg/ml); and group IV, (n=29) ultrasound-guided RSB (ropivacaine 100 mg) combined with PCIA (butorphanol 0.08 µg/ml). Outcomes included visual analogue scale (VAS) scores (0-10) of incisional pain (defined as superficial pain on the abdominal wall) and visceral pain (defined as deep, dull pain within the abdomen) at rest and during cough at 2,6,12 and 24 h postoperatively, the dose of butorphanol and sufentanil, the number of PCIA presses, the length of hospital stay and the incidence of postoperative adverse events. Results: Both the rest and cough incisional pain scores were lower during the first 2 and 6 h in group Ⅲ than in group Ⅰ (P＜0.05). Similarly, scores in group Ⅳ were significantly lower than those in group II (P＜0.05). Patients in group I needed more butorphanol as a rescue analgesic for pain relief than did those in group III, and patients in group IV needed less butorphanol as a rescue analgesic for pain relief than did those in group II. From the above pairwise comparisons, it is clear that groups III and IV had lower VAS scores. The VAS scores for visceral pain were lower in group II at 2, 6 and 12 h after surgery than in group I and lower in group IV than in group Ⅲ. Overall, ultrasound-guided RSB combined with PCIA (butorphanol 0. 08 µg/ml) performed the best. Conclusions: Ultrasound-guided RSB combined with butorphanol can provide sufficient pain treatment after SILC than can general anaesthesia combined with sufentanil.

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Physiology of Visceral Pain

Cited by 174 publications

References 241 publications

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Identifying unique subtypes of spinal afferent nerve endings within the urinary bladder of mice

Efficacy of ultrasound-guided rectus sheath block, butorphanol for single-incision laparoscopic cholecystectomy: A prospective, randomized, clinical trial

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