Investigation of the Involvement of the Endocannabinoid System in TENS-Induced Antinociception

Oliveira, Herick Ulisses de; Santos, Rafaela Silva; Malta, Iago Henrique Silva; Pinho, José Phellipe; Almeida, Ana Flávia Santos; Sorgi, Carlos Artério; Peti, Ana Paula Ferranti; Xavier, Gabriela Santos; Reis, Luciana Maria dos; Faccioli, Lúcia Helena; Cruz, Jáder Santos; Ferreira, Ênio; Galdino, Giovane

doi:10.1016/j.jpain.2019.11.009

Cited by 11 publications

(12 citation statements)

References 66 publications

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“…The mechanistic basis that explains the effectiveness of TENS-based analgesia treatment is related to the release of several neuroregulatory substances, especially opioids, gamma-aminobutyric acid, norepinephrine, serotonin, and endocannabinoids [3]. There is evidence that TENS stimulates the release of serotonin in the spinal cord and promotes antinociception in a kaolin-carrageenan-induced inflammatory pain model [8], which may represent an important mechanism of TENS-induced antinociception.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to cannabidiol, non-pharmacological therapies are also used to treat pain as they are cost-effective, easy-to-use and almost free of adverse effects. Accordingly, transcutaneous electrical nerve stimulation (TENS) is used to induce analgesia with the advantage of not inducing side effects when properly administered [3]. Therefore, TENS can be considered a reliable resource in pain management [3].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice

et al. 2023

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Objectives Pain is the most common cause of seeking healthcare and the leading cause of disability worldwide. Although cannabidiol and transcutaneous electrical nerve stimulation (TENS) are effective and safe strategies for treating chronic pain, the combined effect of these interventions remains overlooked. To compare the isolated and combined effect of cannabidiol and TENS in the treatment of experimental neuropathic and inflammatory pain. Methods Swiss mice were subjected to chronic constriction injury (CCI)-induced neuropathic or carrageenan-induced inflammatory pain models. Cannabidiol or TENS alone and the combination of these therapies were administered once. The nociceptive threshold was measured by the von Frey test. IL-1β, TNF-α and IL-10 cytokine levels were measured by ELISA from spinal cord samples. Results Combined, cannabidiol and TENS potentiate antinociception only in neuropathic pain. IL-1β and TNF-α levels were similarly reduced when TENS or cannabidiol were administered alone or in combination. However, only cannabidiol and TENS combined increased IL-10 levels. Conclusions Our findings indicated TENS and cannabidiol combined were effective in potentiating antinociception in a neuropathic pain model, an effect potentially associated with spinal IL-10 upregulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice

et al. 2023

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“…LF TENS increases the release of serotonin, which produces analgesia through 5-HT2A and 5-HT3 serotonin receptors in the spinal cord [ 20 ]. The blockade of cannabinoid receptor 1 (CB1) in the PAG reversed both low- and high-frequency TENS analgesia and was associated with an increase in CB1 receptor expression [ 21 ]. Thus, TENS produces analgesia by activating endogenous inhibitory mechanisms in the central nervous system, involving opioid, GABA, serotonin, muscarinic, and cannabinoid receptors.…”

Section: Neurotransmitters and Receptors That Mediate Tens Analgesiamentioning

confidence: 99%

“…A few studies have shown peripheral effects of TENS. HF TENS reduces tissue-injury increases in substance P in dorsal root ganglia neurons [ 38 ], blockade of peripheral opioid receptors prevents the analgesia produced by LF and HF TENS [ 44 , 45 , 46 ], and blockade of CB1 receptors prevents production of analgesia by HF and LF TENS [ 21 ]. Thus, TENS may also alter excitability of peripheral nociceptors to reduce afferent input to the central nervous system.…”

Section: Peripheral Mechanisms Of Tensmentioning

confidence: 99%

Using TENS for Pain Control: Update on the State of the Evidence

et al. 2022

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Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention used in the treatment of acute and chronic pain conditions. The first clinical studies on TENS were published over 50 years ago, when effective parameters of stimulation were unclear and clinical trial design was in its infancy. Over the last two decades, a better understanding of the mechanisms underlying TENS efficacy has led to the development of an adequate dose and has improved outcome measure utilization. The continued uncertainty about the clinical efficacy of TENS to alleviate pain, despite years of research, is related to the quality of the clinical trials included in systematic reviews. This summary of the evidence includes only trials with pain as the primary outcome. The outcomes will be rated as positive (+), negative (−), undecided (U), or equivalent to other effective interventions (=). In comparison with our 2014 review, there appears to be improvement in adverse events and parameter reporting. Importantly, stimulation intensity has been documented as critical to therapeutic success. Examinations of the outcomes beyond resting pain, analgesic tolerance, and identification of TENS responders remain less studied areas of research. This literature review supports the conclusion that TENS may have efficacy for a variety of acute and chronic pain conditions, although the magnitude of the effect remains uncertain due to the low quality of existing literature. In order to provide information to individuals with pain and to clinicians treating those with pain, we suggest that resources for research should target larger, high-quality clinical trials including an adequate TENS dose and adequate timing of the outcome and should monitor risks of bias. Systematic reviews and meta-analyses should focus only on areas with sufficiently strong clinical trials that will result in adequate sample size.

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“…WB widely measures CB1r and CB2r protein alterations, for example, to determine the levels of CB1r protein in the spinal cord and dorsolateral periaqueductal grey matter of rodents [153].…”

Section: Protein Level Alterationsmentioning

confidence: 99%

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro

Gasparyan

Navarrete

et al. 2022

IJMS

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The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

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Investigation of the Involvement of the Endocannabinoid System in TENS-Induced Antinociception

Cited by 11 publications

References 66 publications

Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice

Synergistic effect of cannabidiol and transcutaneous electrical nerve stimulation on neuropathic and inflammatory pain in mice

Using TENS for Pain Control: Update on the State of the Evidence

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

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