pain transmission
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2022 ◽  
Vol 9 (1) ◽  
pp. 55
Author(s):  
Carmelina D'Arro

Medical and dental procedures present a minefield of opportunities for pain and anxiety. Many procedures for diagnosis, treatment, and palliation are performed either without comfort measures at all or with sedation/anesthesia. Yet, there are many ways of decreasing patients’ procedural pain and anxiety and of increasing physical and psychological comfort. Gate control theory explains how we can close the gate on pain transmission (and minimize opening the gate) through non-pharmacological means. An exploration of several bottom-up and top-down interventions will be discussed including breathing, mindfulness, gradual exposure, non-pain stimuli, distraction, touch, and postoperative communications. Interventions will be illustrated with pictures and short videos in the dental setting.


Author(s):  
Mengmeng Zhou ◽  
Jinrong Wu ◽  
Hongen Chang ◽  
Yuxin Fang ◽  
Di Zhang ◽  
...  

Neurology ◽  
2021 ◽  
Vol 98 (1 Supplement 1) ◽  
pp. S22.3-S23
Author(s):  
Michael F. La Fountaine ◽  
Anthony Testa

ObjectiveDetermine whether single nucleotide polymorphisms (SNPs) of the calcitonin gene-related polypeptide (CGRP)-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) are related to headache burden during the first week after concussion.BackgroundPost-traumatic headache is a commonly reported symptom after concussion. SNPs related to CGRP are involved in the pathogenesis of migraine headaches and contribute to pain transmission and neurogenic inflammation. It is unclear in concussed persons if the headache burden is associated with genetic variations related to CGRP.Design/MethodsA prospective study was performed in 34 concussed athletes (gender: 23 female, 11 male; age: 20 ± 1 years; height: 1.75 ± 0.12 meters; weight: 73 ± 14 kilograms). Participants completed the symptom evaluation checklist from the SCAT3 within 48 hours of injury (V1), and 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0–6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were summed. The area under-the-curve (AUC) was computed for the early (EHB: V1 to V2) and late (LHB: V2 to V3) burden of headache-related symptoms. A saliva sample was obtained and a commercial laboratory identified the genotype for CALCA (rs3781719) and RAMP1 (rs10185142) using PMR-array. RAMP1 genotypes RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) genotypes were dichotomized (T+, T−, and A+, A− respectively) and concatenated (T + A+, T + A−, T−A+, T-A−) for analyses.ResultsA significant difference for EHB (p = 0.003, partial η2 = 0.417) was present across RAMP1+CALCA genotypes, but not for the LHB. The T + A+ subgroup had a significantly elevated EHB compared to the all-other subgroups (p < 0.05: T + A + [n = 16]: 31.6 ± 2.6; T + A − [n = 9]: 17.7 ± 3.6; T−A+ [n = 8]: 18.4 ± 3.7; T−A-[n = 1]: 0.0 ± 0.0). Gender served as a covariate and diagnosed concussion history had no impact.ConclusionsThe current analysis provides a proof-of-concept to suggest that the combined T + A+ genoset from RAMP1+CALCA are associated with a greater headache burden in the first 4 days after concussion injury.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6168
Author(s):  
Kornél Király ◽  
Dávid Á. Karádi ◽  
Ferenc Zádor ◽  
Amir Mohammadzadeh ◽  
Anna Rita Galambos ◽  
...  

The current protocols for neuropathic pain management include µ-opioid receptor (MOR) analgesics alongside other drugs; however, there is debate on the effectiveness of opioids. Nevertheless, dose escalation is required to maintain their analgesia, which, in turn, contributes to a further increase in opioid side effects. Finding novel approaches to effectively control chronic pain, particularly neuropathic pain, is a great challenge clinically. Literature data related to pain transmission reveal that angiotensin and its receptors (the AT1R, AT2R, and MAS receptors) could affect the nociception both in the periphery and CNS. The MOR and angiotensin receptors or drugs interacting with these receptors have been independently investigated in relation to analgesia. However, the interaction between the MOR and angiotensin receptors has not been excessively studied in chronic pain, particularly neuropathy. This review aims to shed light on existing literature information in relation to the analgesic action of AT1R and AT2R or MASR ligands in neuropathic pain conditions. Finally, based on literature data, we can hypothesize that combining MOR agonists with AT1R or AT2R antagonists might improve analgesia.


2021 ◽  
Vol 12 ◽  
Author(s):  
Annamaria Fidilio ◽  
Margherita Grasso ◽  
Rita Turnaturi ◽  
Giuseppe Caruso ◽  
Federica Maria Spitale ◽  
...  

Neuropathic pain is one of the most disabling forms of chronic pain and it is characterized by hyperalgesia and allodynia linked to an aberrant processing of pain transmission and to neuroinflammation. Transforming growth factor-β1 (TGF-β1) is an anti-inflammatory cytokine, which protects against neuroinflammation. It has been demonstrated that TGF-β1 and opioid receptors signalling crosstalk results in an improvement of endogenous opioid analgesia, but it is not known whether mu opioid peptide receptor (MOPr) or delta opioid peptide receptor (DOPr) agonists can positively modulate TGF-β1 pathway. In the present study, we examined the correlation between anti-allodynic effect of LP2, a dual-target MOPr/DOPr agonist, and TGF-β1 signalling in the chronic constriction injury (CCI) model. We detected a significant decrease of active TGF-β1 and of its type II receptor TGFβ-R2 levels in the spinal cord from CCI rats and a selective deficit of TGF-β1 in microglia cells both at days 11 and 21 post-ligature, as assessed by immunofluorescence analysis. LP2, when administered from the 11 days post-ligature to 21 days, was able to reduce CCI-induced mechanical allodynia by rescue of TGF-β1 and TGFβ-R2 levels. Our data suggest that the rescue of TGF-β1 signalling by dual-target MOPr/DOPr agonist LP2 could be mediated by DOPr activation in spinal microglia, thus the dual-target approach could represent a novel pharmacological approach to increase the analgesic efficacy of MOPr agonists.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4594
Author(s):  
Jialun Wang ◽  
Yu Chen ◽  
Xihan Li ◽  
Xiaoping Zou

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor–neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Eun Kim ◽  
Min Kyung Kim ◽  
Sang-il Suh ◽  
Ji Hyun Kim

Abstract Background Recent resting-state fMRI studies demonstrated functional dysconnectivity within the central pain matrix in migraineurs. This study aimed to investigate the spatial distribution and amplitude of low-frequency oscillations (LFOs) using fractional amplitude of low-frequency fluctuation (fALFF) analysis in migraine patients without aura, and to examine relationships between regional LFOs and clinical variables. Methods Resting-state fMRI data were obtained and preprocessed in 44 migraine patients without aura and 31 matched controls. fALFF was computed according to the original method, z-transformed for standardization, and compared between migraineurs and controls. Correlation analysis between regional fALFF and clinical variables was performed in migraineurs as well. Results Compared with controls, migraineurs had significant fALFF increases in bilateral ventral posteromedial (VPM) thalamus and brainstem encompassing rostral ventromedial medulla (RVM) and trigeminocervical complex (TCC). Regional fALFF values of bilateral VPM thalamus and brainstem positively correlated with disease duration, but not with migraine attack frequency or Migraine Disability Assessment Scale score. Conclusions We have provided evidence for abnormal LFOs in the brainstem including RVM/TCC and thalamic VPM nucleus in migraine without aura, implicating trigeminothalamic network oscillations in migraine pathophysiology. Our results suggest that enhanced LFO activity may underpin the interictal trigeminothalamic dysrhythmia that could contribute to the impairments of pain transmission and modulation in migraine. Given our finding of increasing fALFF in relation to increasing disease duration, the observed trigeminothalamic dysrhythmia may indicate either an inherent pathology leading to migraine headaches or a consequence of repeated attacks on the brain.


2021 ◽  
Author(s):  
Kazuhiko Nishida ◽  
Shinji Matsumura ◽  
Takuya Kobayashi

Spinal dorsal horn plays crucial roles in the transmission and processing of somatosensory information. Although spinal neural circuits which process several distinct types of cutaneous sensation have been extensively studied, those responsible for visceral pain transmission remain poorly understood. In the present study, we analyzed the dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) model mice to characterize the spinal dorsal horn neurons involved in visceral pain transmission. DSS-treated mice exhibited increased abdominal licking behavior, suggestive of experiencing visceral pain. Immunostaining of c-fos, a marker indicating neuronal activity, demonstrated that numerous c-fos-positive cells were found bilaterally in the lumbosacral spinal dorsal horn, and their distribution was particularly abundant in the shallow dorsal horn. Neurochemical characterization of these neurons revealed that the percentage of the POU transcription factor Brn3a-positive neurons among the c-fos-positive neurons in the shallow dorsal horn was 30-40% in DSS-treated mice, which was significantly higher than that in the somatic pain model mice. We further demonstrated by neuronal tracing that within the shallow dorsal horn, Brn3a-positive neurons are represented more highly in spino-solitary projection neurons than in spino-parabrachial projection ones. These results raised the possibility that Brn3a-positive spinal dorsal horn neurons make a large contribution to visceral pain transmission, and part of which was mediated through spino-solitary pathway.


Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2260
Author(s):  
Letizia Zanetti ◽  
Maria Regoni ◽  
Elena Ratti ◽  
Flavia Valtorta ◽  
Jenny Sassone

AMPA receptors (AMPARs) are ionotropic glutamate receptors that play a major role in excitatory neurotransmission. AMPARs are located at both presynaptic and postsynaptic plasma membranes. A huge number of studies investigated the role of postsynaptic AMPARs in the normal and abnormal functioning of the mammalian central nervous system (CNS). These studies highlighted that changes in the functional properties or abundance of postsynaptic AMPARs are major mechanisms underlying synaptic plasticity phenomena, providing molecular explanations for the processes of learning and memory. Conversely, the role of AMPARs at presynaptic terminals is as yet poorly clarified. Accruing evidence demonstrates that presynaptic AMPARs can modulate the release of various neurotransmitters. Recent studies also suggest that presynaptic AMPARs may possess double ionotropic-metabotropic features and that they are involved in the local regulation of actin dynamics in both dendritic and axonal compartments. In addition, evidence suggests a key role of presynaptic AMPARs in axonal pathology, in regulation of pain transmission and in the physiology of the auditory system. Thus, it appears that presynaptic AMPARs play an important modulatory role in nerve terminal activity, making them attractive as novel pharmacological targets for a variety of pathological conditions.


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