scholarly journals Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Nav1.8 β1 Subunit of Sensory Neurons

2019 ◽  
Vol 9 ◽  
Author(s):  
Xiao-Long Zhang ◽  
Xian-Ying Cao ◽  
Ren-Chun Lai ◽  
Man-Xiu Xie ◽  
Wei-An Zeng
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons

scholarly journals Sensory Neurons, Ion Channels, Inflammation and the Onset of Neuropathic Pain

2012 ◽  
Vol 39 (4) ◽  
pp. 416-435 ◽  
Author(s):  
Patrick L. Stemkowski ◽  
Peter A. Smith
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Pain Management ◽  
Sensory Neurons ◽  
Inflammatory Mediators ◽  
Primary Afferents ◽  
Ectopic Activity ◽  
Management Procedures

Neuropathic pain often fails to respond to conventional pain management procedures. here we review the aetiology of neuropathic pain as would result from peripheral neuropathy or injury. We show that inflammatory mediators released from damaged nerves and tissue are responsible for triggering ectopic activity in primary afferents and that this, in turn, provokes increased spinal cord activity and the development of ‘central sensitization’. Although evidence is mounting to support the role of interleukin-1β, prostaglandins and other cytokines in the onset of neuropathic pain, the clinical efficacy of drugs which antagonize or prevent the actions of these mediators is yet to be determined. basic science findings do, however, support the use of pre-emptive analgesia during procedures which involve nerve manipulation and the use of anti-inflammatory steroids as soon as possible following traumatic nerve injury.

scholarly journals Neuropathic Pain Develops Normally in Mice Lacking both Nav1.7 and Nav1.8

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-24 ◽  
Author(s):  
Mohammed A Nassar ◽  
Alessandra Levato ◽  
L Caroline Stirling ◽  
John N Wood
Keyword(s):  
Neuropathic Pain ◽  
Sodium Channels ◽  
Sensory Neurons ◽  
Inflammatory Pain ◽  
Pain Thresholds ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Pain Symptoms ◽  
Α Subunits

Two voltage gated sodium channel α-subunits, Nav1.7 and Nav1.8, are expressed at high levels in nociceptor terminals and have been implicated in the development of inflammatory pain. Mis-expression of voltage-gated sodium channels by damaged sensory neurons has also been implicated in the development of neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain. Here we show that deleting Nav1.7 has no effect on the development of neuropathic pain. Double knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic pain, despite a lack of inflammatory pain symptoms and altered mechanical and thermal acute pain thresholds. These studies demonstrate that, in contrast to the highly significant role for Nav1.7 in determining inflammatory pain thresholds, the development of neuropathic pain does not require the presence of either Nav1.7 or Nav1.8 alone or in combination.

scholarly journals Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

2020 ◽  
Vol 14 ◽  
Author(s):  
Emily L. Tran ◽  
LaTasha K. Crawford
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Sensory Ganglia ◽  
Intercellular Signaling ◽  
Sensory Afferents ◽  
Pain Mechanisms ◽  
Wide Range ◽  
Cell Type Specific

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.

scholarly journals Neuronal Dual Leucine Zipper Kinase Mediates Inflammatory and Nociceptive Responses in Cyclophosphamide-Induced Cystitis

2021 ◽  
pp. 1-10
Author(s):  
Chen Jiang ◽  
Weilin Fang ◽  
Tingting Lv ◽  
Yinjun Gu ◽  
Jianwei Lv
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Neurogenic Inflammation ◽  
Leucine Zipper ◽  
Nociceptive Behavior ◽  
Bladder Pain ◽  
Pharmacological Inhibition ◽  
Nociceptive Responses ◽  
Bladder Pathology

Interstitial cystitis is associated with neurogenic inflammation and neuropathic bladder pain. Dual leucine zipper kinase (DLK) expressed in sensory neurons is implicated in neuropathic pain. We hypothesized that neuronal DLK is involved in the regulation of inflammation and nociceptive behavior in cystitis. Mice deficient in DLK in sensory neurons (cKO) were generated by crossing DLK floxed mice with mice expressing Cre recombinase under Advillin promoter. Cystitis was induced by cyclophosphamide (CYP) administration in mice. Nociceptive behavior, bladder inflammation, and pathology were assessed following cystitis induction in control and cKO mice. The role of DLK in CYP-induced cystitis was further determined by pharmacological inhibition of DLK with GNE-3511. Deletion of neuronal DLK attenuated CYP-induced pain-like nociceptive behavior and suppressed histamine release from mast cells, neuronal activation in the spinal cord, and bladder pathology. Mice deficient in neuronal DLK also showed reduced inflammation induced by CYP and reduced c-Jun activation in the dorsal root ganglia (DRG). Pharmacological inhibition of DLK with GNE-3511 recapitulated the effects of neuronal DLK depletion in CYP treatment mice. Our study suggests that DLK is a potential target for the treatment of neuropathic pain and bladder pathology associated with cystitis.

Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy

2016 ◽  
Vol 96 ◽  
pp. 294-311 ◽  
Author(s):  
Christine Altmann ◽  
Stefanie Hardt ◽  
Caroline Fischer ◽  
Juliana Heidler ◽  
Hee-Young Lim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons

Emerging Role of microRNA in Neuropathic Pain

2016 ◽  
Vol 17 (4) ◽  
pp. 336-344 ◽  
Author(s):  
Pu Jiangpan ◽  
Meng Qingsheng ◽  
Yang Zhiwen ◽  
Zhu Tao
Keyword(s):  
Neuropathic Pain

scholarly journals A9 DORSAL ROOT GANGLIA NEURONAL RESPONSES AND SUBSTANCE P PRODUCTION ARE HIGHER IN MALE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 10-11
Author(s):  
J Pujo ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Abdominal Pain ◽  
Substance P ◽  
Gut Microbiota ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Response ◽  
Neuronal Responses ◽  
Visceral Sensitivity ◽  
Germ Free

Abstract Background Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as women report more abdominal pain than men. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood. Aims To investigate the role of gut microbiota and sex in abdominal pain. Methods We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventionally raised (SPF) or germ-free (GF) mice (7–18 weeks old). To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered i) the percentage of responding neurons ii) the intensity of the neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by a mixture of G-protein coupled receptors agonist (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next measured the neuronal production of substance P and calcitonin gene-related peptide (CGRP), two neuropeptides associated with nociception, in response to capsaicin (1.25µM) or GPCR agonists (100µM) by ELISA and EIA, respectively. Results The percentage of neurons responding to capsaicin and GPCR agonists was similar in male and female SPF and GF mice. However, the intensity of the neuronal response was higher in SPF male compared to SPF female in response to capsaicin (125nM: p=0.0336; 1.25µM: p=0.033) but not to GPCR agonists. Neuronal activation was similar in GF and SPF mice of both sexes after administration of capsaicin or GPCR agonists. Furthermore, substance P and CGRP production by sensory neurons induced by capsaicin or GPCR agonists was similar in SPF and GF mice, regardless of sex. However, while the response to capsaicin was similar, the GPCR agonists-induced production of substance P was higher in SPF male mice compared to SPF females (p=0.003). The GPCR agonists-induced production of CGRP was similar in SPF male and female mice. Conclusions Our data suggest that at the level of DRG neurons, the absence of gut microbiota does not predispose to visceral hypersensitivity. The intensity of DRG neuronal responses to capsaicin and the GPCR agonists-induced production of substance P are higher in male compared to female mice, in contrast to previously published studies in various models of acute and chronic pain. Further studies are thus needed to investigate the role of sex in visceral sensitivity. Funding Agencies CIHR

scholarly journals Pre-motor versus motor cerebral cortex neuromodulation for chronic neuropathic pain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Igor Lavrov ◽  
Timur Latypov ◽  
Elvira Mukhametova ◽  
Brian Lundstrom ◽  
Paola Sandroni ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cerebral Cortex ◽  
Motor Cortex ◽  
Initial Assessment ◽  
Motor Cortex Stimulation ◽  
Chronic Neuropathic Pain ◽  
Long Term Effect ◽  
Stimulation Of

AbstractElectrical stimulation of the cerebral cortex (ESCC) has been used to treat intractable neuropathic pain for nearly two decades, however, no standardized approach for this technique has been developed. In order to optimize targeting and validate the effect of ESCC before placing the permanent grid, we introduced initial assessment with trial stimulation, using a temporary grid of subdural electrodes. In this retrospective study we evaluate the role of electrode location on cerebral cortex in control of neuropathic pain and the role of trial stimulation in target-optimization for ESCC. Location of the temporary grid electrodes and location of permanent electrodes were evaluated in correlation with the long-term efficacy of ESCC. The results of this study demonstrate that the long-term effect of subdural pre-motor cortex stimulation is at least the same or higher compare to effect of subdural motor or combined pre-motor and motor cortex stimulation. These results also demonstrate that the initial trial stimulation helps to optimize permanent electrode positions in relation to the optimal functional target that is critical in cases when brain shift is expected. Proposed methodology and novel results open a new direction for development of neuromodulation techniques to control chronic neuropathic pain.

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2021 ◽  
Author(s):  
Xiaohua Fan ◽  
Chuanwei Wang ◽  
Junting Han ◽  
Xinli Ding ◽  
Shaocan Tang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root
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