scholarly journals Endogenous Analgesia, Dependence, and Latent Pain Sensitization

2014 ◽  
pp. 283-325 ◽  
Author(s):  
Bradley K. Taylor ◽  
Gregory Corder
Keyword(s):  
Pain Sensitization ◽  
Endogenous Analgesia

Insight into Pain Modulation: Nociceptors Sensitization and Therapeutic Targets

2019 ◽  
Vol 20 (7) ◽  
pp. 775-788 ◽  
Author(s):  
Amna Khan ◽  
Salman Khan ◽  
Yeong Shik Kim
Keyword(s):  
Ion Channels ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Experimental Models ◽  
Pain Modulation ◽  
Metabotropic Glutamate ◽  
Pain Sensitization ◽  
Neurokinin 1 ◽  
Pain Transduction

Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli lead to the activation of receptors and further neuronal processing produces the sensation of pain. Numerous types of receptors are activated in pain sensation which vary in their signaling pathway. These signaling pathways can be regarded as a site for modulation of pain by targeting the pain transduction molecules to produce analgesia. On the basis of their anatomic location, transient receptor potential ion channels (TRPV1, TRPV2 and TRPM8), Piezo 2, acid-sensing ion channels (ASICs), purinergic (P2X and P2Y), bradykinin (B1 and B2), α-amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), metabotropic glutamate (mGlu), neurokinin 1 (NK1) and calcitonin gene-related peptide (CGRP) receptors are activated during pain sensitization. Various inhibitors of TRPV1, TRPV2, TRPM8, Piezo 2, ASICs, P2X, P2Y, B1, B2, AMPA, NMDA, mGlu, NK1 and CGRP receptors have shown high therapeutic value in experimental models of pain. Similarly, local inhibitory regulation by the activation of opioid, adrenergic, serotonergic and cannabinoid receptors has shown analgesic properties by modulating the central and peripheral perception of painful stimuli. This review mainly focused on various classes of nociceptors involved in pain transduction, transmission and modulation, site of action of the nociceptors in modulating pain transmission pathways and the drugs (both clinical and preclinical data, relevant to targets) alleviating the painful stimuli by exploiting nociceptor-specific channels and receptors.

scholarly journals Sympathetic and sensory nerve fiber function in multiple system atrophy and idiopathic Parkinson’s disease

2021 ◽  
Author(s):  
Heidrun H. Krämer ◽  
Cora Rebhorn ◽  
Christian Geber ◽  
Frank Birklein
Keyword(s):  
Detection Threshold ◽  
Sensory Nerve ◽  
Research Network ◽  
Sensory Testing ◽  
Sympathetic Function ◽  
Autonomic Testing ◽  
German Research ◽  
Pain Sensitization ◽  
Mechanical Detection ◽  
Mechanical Pain Thresholds

Abstract Objective To explore small fiber somatosensory and sympathetic function in PD and MSA. Methods We recruited 20 PD patients (7 women, median age 65.5 years; IQR 54.75–70.0), 10 MSA patients (4 women; median age 68 years; IQR 66.25–74.0), and 10 healthy subjects (HC; 4 women, median age 68; IQR 59.0–71.0 years). Autonomic testing included forehead cooling, intradermal microdialysis of norepinephrine (NE; 10–5; 10–6; 10–7; and 10–8), and orthostatic hypotension (OH); somatosensory testing included quantitative sensory testing (QST) according to the protocol of the German Research Network on Neuropathic Pain (DFNS). Results OH occurred more frequently in PD (p = 0.018) and MSA (p = 0.002) compared to HC. Vasoconstriction responses were stronger in PD compared to MSA during forehead cooling (p = 0.044) and microdialysis of physiologically concentrated NE solutions (10–7; 10–8; p = 0.017). PD and MSA had impaired cold (PD: p < 0.01; MSA: p < 0.05) and warm detection thresholds (PD and MSA, both p < 0.05). The mechanical detection threshold was higher in PD (p < 0.01). Conversely, mechanical pain thresholds were decreased in PD and MSA (both p < 0.001), indicating mechanical hyperalgesia. Conclusion In contrast to MSA, we found evidence of peripheral adrenoreceptor hypersensitivity in PD, probably caused by peripheral sympathetic denervation. Sensory testing revealed peripheral neuropathy and central pain sensitization in PD and MSA. Jointly, our data demonstrate autonomic and somatosensory dysfunction in PD and MSA.

Specialized, pro-resolving mediators as potential therapeutic agents for alleviating fibromyalgia symptomatology

Pain Medicine ◽  
2021 ◽  
Author(s):  
Gregory Livshits ◽  
Alexander Kalinkovich
Keyword(s):  
Animal Experiments ◽  
Therapeutic Agents ◽  
Treatment Modalities ◽  
Inflammatory Factors ◽  
Gut Dysbiosis ◽  
Unsuccessful Treatment ◽  
Pain Sensitization ◽  
Novel Strategy ◽  
Inflammation Resolution

Abstract Objective To present a hypothesis on a novel strategy in the treatment of fibromyalgia (FM). Design A narrative review. Setting FM as a disease remains a challenging concept for numerous reasons, including undefined etiopathogenesis, unclear triggers and unsuccessful treatment modalities. We hypothesize that the inflammatome, the entire set of molecules involved in inflammation, acting as a common pathophysiological instrument of gut dysbiosis, sarcopenia, and neuroinflammation, is one of the major mechanisms underlying FM pathogenesis. In this setup, dysbiosis is proposed as the primary trigger of the inflammatome, sarcopenia as the peripheral nociceptive source, and neuroinflammation as the central mechanism of pain sensitization, transmission and symptomatology of FM. Whereas neuroinflammation is highly-considered as a critical deleterious element in FM pathogenesis, the presumed pathogenic roles of sarcopenia and systemic inflammation remain controversial. Nevertheless, sarcopenia-associated processes and dysbiosis have been recently detected in FM individuals. The prevalence of pro-inflammatory factors in the cerebrospinal fluid and blood has been repeatedly observed in FM individuals, supporting an idea on the role of inflammatome in FM pathogenesis. As such, failed inflammation resolution might be one of the underlying pathogenic mechanisms. In accordance, the application of specialized, inflammation pro-resolving mediators (SPMs) seems most suitable for this goal. Conclusions The capability of various SPMs to prevent and attenuate pain has been repeatedly demonstrated in laboratory animal experiments. Since SPMs suppress inflammation in a manner that does not compromise host defense, they could be attractive and safe candidates for the alleviation of FM symptomatology, probably in combination with anti-dysbiotic medicine.

Could Schizophrenia Be a Refractory Condition to Central Pain Sensitization?

2014 ◽  
pp. 157-171
Author(s):  
Sylvain Grignon ◽  
Katherine Stavro ◽  
Stéphane Potvin
Keyword(s):  
Central Pain ◽  
Pain Sensitization

scholarly journals Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulia Puja ◽  
Balazs Sonkodi ◽  
Rita Bardoni
Keyword(s):  
Central Pain ◽  
Spinal Trigeminal Nucleus ◽  
Trigeminal Nucleus ◽  
Ocular Pain ◽  
Cellular Mechanisms ◽  
New Techniques ◽  
Functional Changes ◽  
Corneal Inflammation ◽  
Pain Sensitization ◽  
Trigeminal Nerves

Persistent ocular pain caused by corneal inflammation and/or nerve injury is accompanied by significant alterations along the pain axis. Both primary sensory neurons in the trigeminal nerves and secondary neurons in the spinal trigeminal nucleus are subjected to profound morphological and functional changes, leading to peripheral and central pain sensitization. Several studies using animal models of inflammatory and neuropathic ocular pain have provided insight about the mechanisms involved in these maladaptive changes. Recently, the advent of new techniques such as optogenetics or genetic neuronal labelling has allowed the investigation of identified circuits involved in nociception, both at the spinal and trigeminal level. In this review, we will describe some of the mechanisms that contribute to the perception of ocular pain at the periphery and at the spinal trigeminal nucleus. Recent advances in the discovery of molecular and cellular mechanisms contributing to peripheral and central pain sensitization of the trigeminal pathways will be also presented.

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