Richard Traub - Academia.edu (original) (raw)

Papers by Richard Traub

BioMed Research International, Oct 10, 2018

Journal of Neurophysiology, 1988

1. Recordings were made from individual sensory neurons with an A-delta peripheral conduction vel... more 1. Recordings were made from individual sensory neurons with an A-delta peripheral conduction velocity, either intrasomally in the L7 dorsal root ganglion, or extracellularly in Lissauer's Tract or in the dorsal root close to the root entry zone. The spinal projection of these afferents was assessed by their antidromic response to stimulation of the dorsal columns (DC) or Lissauer's Tract (LT) at the L5/L6 border. The adequate stimulus was also ascertained. 2. A-delta-fibers could be divided into two groups: high-threshold mechanoreceptors from either skin or muscle (HTMRs) and low-threshold mechanoreceptors (LTMs), primarily Down Hairs. A third group of cells recorded intrasomally had broad spikes with shoulders on the downstroke characteristic of A-delta-nociceptors and were so classified provisionally, although no adequate stimulus could be identified. HTMRs and broad spike cells projected either in DC or LT, but LTMs projected only in DC, never in LT. About one-quarter o...

Mass spectrometry imaging (MSI) is a powerful scientific tool for understanding the spatial distr... more Mass spectrometry imaging (MSI) is a powerful scientific tool for understanding the spatial distribution of biochemical compounds in tissue structures. MSI data analysis presents problems due to the large file sizes and computational resource requirements and also due to the complexity of interpreting the raw spectral data. Dimensionality reduction techniques that address the first issue do not necessarily result in readily interpretable features. In this paper, we present non-negative matrix factorization (NMF) as a dimensionality reduction algorithm that reduces the size of MSI datasets by three orders of magnitude with limited loss of information, yielding spatial and spectral components with meaningful correlation to tissue structure. This analysis is demonstrated on an MSI dataset from female Sprague-Dawley rats for an animal model of comorbid visceral pain hypersensitivity (CPH). The significant findings are: 1) High-dimensional MSI data (∼100,000 ions per pixel) was reduced t...

Molecular Pain, 2022

Oxytocin (OT) is recognized as a critical neuropeptide in pain-related disorders. Chronic pain ca... more Oxytocin (OT) is recognized as a critical neuropeptide in pain-related disorders. Chronic pain caused by the comorbidity of temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) is common, but whether OT plays an analgesic role in the comorbidity of TMD and FMS is unknown. Female rats with masseter muscle inflammation combined with 3-day forced swim (FS) stress developed somatic hypersensitivity, which modeled the comorbidity of TMD and FMS. Using this model, the effects of spinal OT administration on mechanical allodynia and thermal hyperalgesia in hindpaws were examined. Furthermore, the protein levels of OT receptors and 5-HT2A receptors in the L4–L5 spinal dorsal horn were analyzed by Western blot. The OT receptor antagonist atosiban and 5-HT2A receptor antagonist ritanserin were intrathecally injected prior to OT injection in the separate groups. Intrathecal injection of 0.125 μg and 0.5 μg OT attenuated the hindpaw hyperalgesia. The expression of OT receptors and 5-...

Epigenetics of Chronic Pain, 2019

Abstract Visceral pain arising from internal organs is a common clinical symptom of multiple dise... more Abstract Visceral pain arising from internal organs is a common clinical symptom of multiple diseases impacting millions of people, yet it is poorly managed. There is evidence that changes in chromatin structure drive stable alterations in gene expression during pain conditions, which underlie several symptoms, including visceral hypersensitivity and anxiety. Epigenetic modulation including DNA methylation, histone modifications, and noncoding RNA regulates visceral pain through enhancing or suppressing receptors of neurotransmitters in the nervous system. Recent findings of epigenetic changes in the peripheral and central nervous system during visceral pain may guide fundamental progress in new treatment targets. In this chapter, we provide a brief overview of still-limited literature that directly implicates epigenetic modifications on visceral pain.

Neuroscience, 2020

Downregulation of spinal 5-HT 2A and 5-HT 2C receptors contributes to somatic hyperalgesia induce... more Downregulation of spinal 5-HT 2A and 5-HT 2C receptors contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, Neuroscience (2020), doi:

Neuropharmacology, 2019

Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechan... more Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT2C receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT2C receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT2C receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT2C receptor antagonist RS-102221 (30 μg/10 μL) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT2C receptors in the spinal cord.

Neural Plasticity, 2019

Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders bu... more 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 regulati...

Processing of Sensory Information in the Superficial Dorsal Horn of the Spinal Cord, 1989

Inflammation and hyperalgesia are common components of many acute and chronic pain conditions inc... more Inflammation and hyperalgesia are common components of many acute and chronic pain conditions including postsurgical acute pain, cancer pain and arthritis. Pathological changes in peripheral nerve produced by trauma, metabolic disorders or viral infections sometimes result in painful neuropathies characterized by spontaneous pain, hyperalgesia and allodynia. Experimental studies in which the effects of peripheral tissue inflammation are compared with the effects of nerve injury on neuronal responsiveness in the peripheral and central nervous systems should provide insights into our understanding of the pathophysiology associated with these acute and chronic pain conditions.

The journal of pain/Journal of pain, Apr 1, 2024

The Journal of Pain, May 1, 2022

Pain

Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are 2 chronic overlapping pai... more Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are 2 chronic overlapping pain conditions (COPCs) that present with significant comorbidity. Both conditions are more prevalent in women and are exacerbated by stress. While peripheral mechanisms might contribute to pain hypersensitivity for each individual condition, mechanisms underlying the comorbidity are poorly understood, complicating pain management when multiple conditions are involved. In this study, longitudinal behavioral and functional MRI-based brain changes have been identified in an animal model of TMD-like pain (masseter muscle inflammation followed by stress) that induces de novo IBS-like comorbid visceral pain hypersensitivity in rats. In particular, data indicate that increased activity in the insula and regions of the reward and limbic systems are associated with more pronounced and longer-lasting visceral pain behaviors in female rats, while the faster pain resolution in male rats may be due to ...

The Journal of Pain, 2021

Chronic Overlapping Pain Conditions, including irritable bowel syndrome (IBS) and temporomandibul... more Chronic Overlapping Pain Conditions, including irritable bowel syndrome (IBS) and temporomandibular disorder (TMD), represent a group of idiopathic pain conditions that likely have peripheral and central mechanisms contributing to their pathology, but are poorly understood. These conditions are exacerbated by stress and have a female predominance. The presence of one condition predicts the presence or development of additional conditions, making this a significant pain management problem. The current study was designed to determine if the duration and magnitude of peripheral sensitization and spinal central sensitization differs between restraint stress-induced visceral hypersensitivity (SIH) and chronic comorbid pain hypersensitivity (CPH; stress during pre-existing orofacial pain). SIH in female rats, as determined by the visceromotor response, persisted at least four but resolved by seven weeks. In contrast, CPH persisted at least seven weeks. Surprisingly, colonic afferents in both SIH and CPH rats were sensitized at seven weeks. CPH rats also had referred pain through seven weeks, but locally anesthetizing the colon only attenuated the referred pain through four weeks, suggesting a transition to colonic afferent independent central sensitization. Different phenotypes of dorsal horn neurons were sensitized in the CPH rats seven weeks post stress compared to four weeks or SIH rats. The current study suggests differential processing of colonic afferent input to the lumbosacral spinal cord contributes to visceral hypersensitivity during comorbid chronic pain conditions. Perspective: Chronic Overlapping Pain Conditions represent a unique challenge in pain management. The diverse nature of peripheral organs hinders a clear understanding of underlying mechanisms accounting for the comorbidity. This study highlights a mismatch between the condition-dependent behavior and peripheral and spinal mechanisms that contribute to visceral pain hypersensitivity.

Molecular Pain, 2016

Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associat... more Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stressinduced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome.