Neuroimaging of pain: Insights into normal and pathological pain mechanisms

The spinal dorsal horn and its equivalent structure in the brainstem constitute the first sites of synaptic integration in the pain pathway. A huge body of literature exists on alterations in spinal nociceptive signal processing that contribute to the generation of exaggerated pain states and hence to what is generally known as “central sensitization.” Such mechanisms include changes in synaptic efficacy or neuronal excitability, which can be evoked by intense nociceptive stimulation or by inflammatory or neuropathic insults. Some of these changes cause alterations in the functional organization of dorsal horn sensory circuits, leading to abnormal pathological pain sensations. This article reviews the present state of this knowledge. It does not cover the contributions of astrocytes and microglia in detail as their functions are the subject of a separate chapter.

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An evolutionary medicine perspective on pain and its disorders

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0288 ◽

2019 ◽

Vol 374 (1785) ◽

pp. 20190288 ◽

Cited By ~ 4

Author(s):

Randolph M. Nesse ◽

Jay Schulkin

Keyword(s):

Chronic Pain ◽

Tissue Damage ◽

Mental States ◽

Preliminary Evidence ◽

Evolutionary Medicine ◽

Smoke Detector ◽

Pain Mechanisms ◽

Trade Offs ◽

Pathological Pain ◽

The Cost

Enormous progress in understanding the mechanisms that mediate pain can be augmented by an evolutionary medicine perspective on how the capacity for pain gives selective advantages, the trade-offs that shaped the mechanisms, and evolutionary explanations for the system's vulnerability to excessive and chronic pain. Syndromes of deficient pain document tragically the utility of pain to motivate escape from and avoidance of situations causing tissue damage. Much apparently excessive pain is actually normal because the cost of more pain is often vastly less than the cost of too little pain (the smoke detector principle). Vulnerability to pathological pain may be explained in part because natural selection has shaped mechanisms that respond adaptively to repeated tissue damage by decreasing the pain threshold and increasing pain salience. The other half of an evolutionary approach describes the phylogeny of pain mechanisms; the apparent independence of different kinds of pain is of special interest. Painful mental states such as anxiety, guilt and low mood may have evolved from physical pain precursors. Preliminary evidence for this is found in anatomic and genetic data. Such insights from evolutionary medicine may help in understanding vulnerability to chronic pain. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

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Glial Cells in Orofacial Pathological Pain Mechanisms

Encyclopedia of Pain ◽

10.1007/978-3-642-28753-4_4924 ◽

2013 ◽

pp. 1374-1378 ◽

Cited By ~ 1

Author(s):

Koichi Iwata ◽

Chen Yu Chiang ◽

Pavel Cherkas

Keyword(s):

Glial Cells ◽

Pain Mechanisms ◽

Pathological Pain

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Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

Neural Plasticity ◽

10.1155/2016/5954890 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

Seung-In Choi ◽

Ji Yeon Lim ◽

Sungjae Yoo ◽

Hyun Kim ◽

Sun Wook Hwang

Keyword(s):

Spinal Cord ◽

Nervous System ◽

Pain Mechanisms ◽

Historical Perspectives ◽

Pain Pathway ◽

Central Regions ◽

The Central Nervous System ◽

Pathological Pain ◽

Synaptic Mechanisms

TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1’s plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies.

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Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain

10.1101/2021.06.15.447407 ◽

2021 ◽

Author(s):

Annemarie Dedek ◽

Jian Xu ◽

Louis-Étienne Lorenzo ◽

Antoine G. Godin ◽

Chaya M. Kandegedara ◽

...

Keyword(s):

Chronic Pain ◽

Sexual Dimorphism ◽

Nmda Receptor ◽

Ex Vivo ◽

Female Rats ◽

Pain Mechanisms ◽

Human Organ ◽

Neuronal Mechanism ◽

Lamina I ◽

Pathological Pain

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn (SDH), direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund′s Adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and NMDA receptor potentiation within SDH neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator, BDNF, failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B, and pGluN2B) in female rats, resulting in no effect of ex vivo BDNF on synaptic NMDA receptor responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in SDH neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDA receptor potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

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Efficacy of Acupuncture on Pain Mechanisms, Inflammatory Responses, and Wound Healing in the Acute Phase of Major Burns: An Experimental Study on Rats

Journal of Burn Care & Research ◽

10.1093/jbcr/irab142 ◽

2021 ◽

Author(s):

Ayse Ebru Abali ◽

Tugrul Cabioglu ◽

Nilufer Bayraktar ◽

Binnaz Handan Ozdemir ◽

Gokhan Moray ◽

...

Keyword(s):

Blood Level ◽

Acute Phase ◽

Interleukin 6 ◽

Inflammatory Responses ◽

Sham Acupuncture ◽

Pain Mechanisms ◽

Burn Wounds ◽

Beta Endorphin ◽

Burn Care ◽

Pathological Pain

Abstract Objectives We investigated acupuncture, a potential contributor for burn-care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Methods Forty male Sprague-Dawley rats were divided into 2 groups. One-hour groups(5 rats/group) were observed for 1 hour and included Sh1(sham/observation), ShA1(sham+acupuncture/observation), Brn1(burn/observation), and BrnA1(burn+acupuncture/observation). Seven-day groups(5 rats/group) were observed for 7 days and included Sh7(sham/observation), ShA7(sham+acupuncture/observation), Brn7(burn/observation), and BrnA7(burn+acupuncture/observation). “Pain-distress scores” were noted daily, acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin-6 and beta-endorphin and skin biopsies for inflammatory-changes and immunohistochemical-staining of interleukin-6 were collected for analysis( P< .05 ). Results In 1-hour groups, interleukin-6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level(P< .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1(P< .05). In all 7-day groups, the agonizing period was 48 to72 hours after burn, with Brn7 most affected(P< .05). Microvessels were multiplied in Brn7group, with significantly higher numbers in burn wounds of BrnA7(P˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin-6 than Brn7 with Brn7-group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels(P˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7(P< .05). Conclusions Acupuncture contributed to management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in acute phase of burn injury in rats.

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