Pain modulation by multi-characteristic opsin sensitization of inhibitory network of brain

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.

Download Full-text

PAIN MODULATION OF SHOCK RESPONSES.

Shock ◽

10.1097/00024382-200206001-00167 ◽

2002 ◽

Vol 17 (Supplement) ◽

pp. 55-56

Author(s):

P. E. Molina

Keyword(s):

Pain Modulation

Download Full-text

A novel clinical applicable bed-side tool for assessing conditioning pain modulation: proof-of-concept

Scandinavian Journal of Pain ◽

10.1515/sjpain-2020-0033 ◽

2020 ◽

Vol 20 (4) ◽

pp. 801-807

Author(s):

Lars Arendt-Nielsen ◽

Jesper Bie Larsen ◽

Stine Rasmussen ◽

Malene Krogh ◽

Laura Borg ◽

...

Keyword(s):

Pain Modulation ◽

Clinical Settings ◽

Proof Of Concept ◽

Finger Nail ◽

Tonic Stimulus ◽

Pressure Pain Thresholds ◽

Custom Made ◽

The Individual ◽

Descending Pain Modulation ◽

Finger Pressure

AbstractBackground and aimsIn recent years, focus on assessing descending pain modulation or conditioning pain modulation (CPM) has emerged in patients with chronic pain. This requires reliable and simple to use bed-side tools to be applied in the clinic. The aim of the present pilot study was to develop and provide proof-of-concept of a simple clinically applicable bed-side tool for assessing CPM.MethodsA group of 26 healthy volunteers participated in the experiment. Pressure pain thresholds (PPT) were assessed as test stimuli from the lower leg before, during and 5 min after delivering the conditioning tonic painful pressure stimulation. The tonic stimulus was delivered for 2 min by a custom-made spring-loaded finger pressure device applying a fixed pressure (2.2 kg) to the index finger nail. The pain intensity provoked by the tonic stimulus was continuously recorded on a 0–10 cm Visual Analog Scale (VAS).ResultsThe median tonic pain stimulus intensity was 6.7 cm (interquartile range: 4.6–8.4 cm) on the 10 cm VAS. The mean PPT increased significantly (P = 0.034) by 55 ± 126 kPa from 518 ± 173 kPa before to 573 ± 228 kPa during conditioning stimulation. When analyzing the individual CPM responses (increases in PPT), a distribution of positive and negative CPM responders was observed with 69% of the individuals classified as positive CPM responders (increased PPTs = anti-nociceptive) and the rest as negative CPM responders (no or decreased PPTs = Pro-nociceptive). This particular responder distribution explains the large variation in the averaged CPM responses observed in many CPM studies. The strongest positive CPM response was an increase of 418 kPa and the strongest negative CPM response was a decrease of 140 kPa.ConclusionsThe present newly developed conditioning pain stimulator provides a simple, applicable tool for routine CPM assessment in clinical practice. Further, reporting averaged CPM effects should be replaced by categorizing volunteers/patients into anti-nociceptive and pro-nociceptive CPM groups.ImplicationsThe finger pressure device provided moderate-to-high pain intensities and was useful for inducing conditioning stimuli. Therefore, the finger pressure device could be a useful bed-side method for measuring CPM in clinical settings with limited time available. Future bed-side studies involving patient populations are warranted to determine the usefulness of the method.

Download Full-text

Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study

Scandinavian Journal of Pain ◽

10.1515/sjpain-2020-0016 ◽

2020 ◽

Vol 20 (4) ◽

pp. 651-661

Author(s):

Paulo E. P. Teixeira ◽

Hanan I. Zehry ◽

Swapnali Chaudhari ◽

Laura Dipietro ◽

Felipe Fregni

Keyword(s):

Knee Osteoarthritis ◽

Pain Intensity ◽

Pain Perception ◽

Small Sample Size ◽

Linear Regression Analysis ◽

Small Sample ◽

Pain Modulation ◽

Clinical Variables ◽

Pain Scores ◽

Intensity Perception

AbstractBackground and aimsPain is a disabling symptom in knee osteoarthritis (KOA) and its underlying mechanism remains poorly understood. Dysfunction of descending pain modulatory pathways and reduced pain inhibition enhance pain facilitation in many chronic pain syndromes but do not fully explain pain levels in chronic musculoskeletal conditions. The objective of this study is to explore the association of clinical variables with pain intensity perception in KOA individuals with varying levels of Conditioned Pain Modulation (CPM) response.MethodsThis is a cross-sectional, exploratory analysis using baseline data of a randomized clinical trial investigating the effects of a non-invasive brain stimulation treatment on the perception of pain and functional limitations due to KOA. Sixty-three subjects with KOA were included in this study. Data on pain perception, mood perception, self-reported depression, physical function, quality of life, and quantitative sensory testing was collected. Multiple linear regression analysis was performed to explore the association between the clinical variables with pain perception for individuals with different levels of CPM response.ResultsFor KOA patients with limited CPM response, perception of limitations at work/other activities due to emotional problems and stress scores were statistically significantly associated with pain scores, F(2, 37) = 7.02, p < 0.01. R-squared = 0.275. For KOA patients with normal CPM response, general health perception scores were statistically significantly associated with pain scores, F(1, 21) = 5.60, p < 0.05. R-squared = 0.2104. Limitations of this study include methodology details, small sample size and study design characteristics.ConclusionsPain intensity perception is associated differently with clinical variables according to the individual CPM response. Mechanistic models to explain pain perception in these two subgroups of KOA subjects are discussed.

Download Full-text