Involvement of Spinal Cannabinoid CB2 Receptors in Exercise-Induced Antinociception

Santos, Rafaela Silva; Sorgi, Carlos Artério; Peti, Ana Paula Ferranti; Veras, Flávio P.; Faccioli, Lúcia Helena; Galdino, Giovane

doi:10.1016/j.neuroscience.2019.08.041

Cited by 22 publications

(17 citation statements)

References 50 publications

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“…Our results indicate that PhAR‐DBH‐Me is a partial activator of CB1 and CB2 receptors, which coincides with the fact that anandamide is a partial agonist at the CB1 and CB2 receptors 42,43 . Both receptors are coupled through G i/o proteins 36 , and CB1 is located on presynaptic terminals, in DRG and dorsal horn neurons 44‐46 , whereas CB2 is highly expressed on glial cells 47‐49 . This cannabinoid receptor distribution explains the antiallodynic effect of synthetic cannabinoids, which in turn acts by inhibiting the hyperexcitability of sensory neurons and the releasing of neurotransmitters such as glutamate or Substance P (SP) that maintains the aberrant circuits of pain 38,45,50 .…”

Section: Discussionsupporting

confidence: 79%

Antiallodynic effect of PhAR‐DBH‐Me involves cannabinoid and TRPV1 receptors

Quiñonez-Bastidas

Palomino-Hernández

López-Ortíz

et al. 2020

Pharmacology Res & Perspec

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Section: Discussionsupporting

confidence: 79%

Antiallodynic effect of PhAR‐DBH‐Me involves cannabinoid and TRPV1 receptors

Quiñonez-Bastidas

Palomino-Hernández

López-Ortíz

et al. 2020

Pharmacology Res & Perspec

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“…Although the nociceptive threshold was not measured in the muscle, the evaluation of mechanical allodynia in the ipsilateral paw of the muscle injury may indirectly suggest a response originating from the trauma-induced injury. Other studies have also found this effect after the administration of inflammatory or allogeneic substances to minimize gastrocnemius muscle pain (Sluka et al, 2001; Radhakrishnan Radhakrishnan et al, 2004;Dos Santos et al, 2019). A possible explanation would be the development of a secondary hyperalgesia (Kehl et al, 2000); in this case, allodynia in response to a central sensitization (Willis and Coggeshall, 1991), which may be induced by spinal microglia activation.…”

Section: Discussionmentioning

confidence: 92%

“…The present study also showed that spinal glial cells are involved in trauma-induced muscle injury, and that resistance exercise training alone or combined with whey protein supplementation prevented the spinal microglial activation. Although there is a study in the literature demonstrating this effect through exercise ( Dos Santos et al, 2019 ), it did not use resistance exercise; however, they did not use resistance exercise. It is known that during exercise, several neurotransmitters are released, that is, endocannabinoids, which may act on specific receptors in the spinal microglia, inhibiting their activation ( Hashemilar et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Resistance Exercise and Whey Protein Supplementation Reduce Mechanical Allodynia and Spinal Microglia Activation After Acute Muscle Trauma in Rats

et al. 2021

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Muscle injury caused by direct trauma to the skeletal muscle is among the main musculoskeletal disorders. Non-pharmacological treatments have been effective in controlling muscle injury–induced pain; however, there are just a few studies in the literature investigating this response. Thus, the present study aimed to evaluate the effect of a resistance exercise training protocol combined or not with whey protein supplementation on mechanical allodynia induced by muscle injury. In addition, we also investigated the involvement of spinal glial cells in this process. For this purpose, male Wistar rats underwent a muscle injury model induced by direct trauma to the gastrocnemius muscle. Mechanical allodynia was measured by a digital von Frey algesimeter test. To evaluate the effect of exercise and/or supplementation on mechanical allodynia, the animals practiced exercises three times a week for 14 days and received supplementation daily for 14 days, respectively. Moreover, the effect of both the participation of spinal glial cells in the muscle injury and the resistance exercise training and/or whey protein supplementation on these cells was also investigated by the Western blot assay. The results demonstrated that resistance exercise training and whey protein supplementation, combined or alone, reduced mechanical allodynia. These treatments also reduced the number of interstitial cells and pro-inflammatory cytokine IL-6 levels in the injured muscle. It was also found that spinal microglia and astrocytes are involved in muscle injury, and that resistance exercise training combined with whey protein supplementation inhibits spinal microglia activation. The results suggest that both resistance exercise training and whey protein supplementation may be effective non-pharmacological treatments to control pain in the muscle after injury induced by acute trauma.

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“…This cannabinoid-induced release of IL-10 by microglia is a phenomenon shared with other areas of the CNS (Correa et al, 2010;Hernangómez et al, 2012). Additionally, activation of CB2R by exercise-induced AEA release reduces levels of TNFα and IL-1β in the spinal cord of mice with carrageenaninduced pain hypersensitivity (dos Santos et al, 2019). In these studies, the reduced release of pro-inflammatory cytokines and increased release of anti-inflammatory cytokines by microglia was associated with reduced pain behavior.…”

Section: Microglial Cb2r In Nociceptive Signalingmentioning

confidence: 86%

Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation

Hoogen

Harding

Davidson

et al. 2022

Front. Neural Circuits

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Chronic pain is a complex sensory, cognitive, and emotional experience that imposes a great personal, psychological, and socioeconomic burden on patients. An estimated 1.5 billion people worldwide are afflicted with chronic pain, which is often difficult to treat and may be resistant to the potent pain-relieving effects of opioid analgesics. Attention has therefore focused on advancing new pain therapies directed at the cannabinoid system because of its key role in pain modulation. Endocannabinoids and exogenous cannabinoids exert their actions primarily through Gi/o-protein coupled cannabinoid CB1 and CB2 receptors expressed throughout the nervous system. CB1 receptors are found at key nodes along the pain pathway and their activity gates both the sensory and affective components of pain. CB2 receptors are typically expressed at low levels on microglia, astrocytes, and peripheral immune cells. In chronic pain states, there is a marked increase in CB2 expression which modulates the activity of these central and peripheral immune cells with important consequences for the surrounding pain circuitry. Growing evidence indicate that interventions targeting CB1 or CB2 receptors improve pain outcomes in a variety of preclinical pain models. In this mini-review, we will highlight recent advances in understanding how cannabinoids modulate microglia function and its implications for cannabinoid-mediated analgesia, focusing on microglia-neuron interactions within the spinal nociceptive circuitry.

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Involvement of Spinal Cannabinoid CB2 Receptors in Exercise-Induced Antinociception

Cited by 22 publications

References 50 publications

Antiallodynic effect of PhAR‐DBH‐Me involves cannabinoid and TRPV1 receptors

Antiallodynic effect of PhAR‐DBH‐Me involves cannabinoid and TRPV1 receptors

Resistance Exercise and Whey Protein Supplementation Reduce Mechanical Allodynia and Spinal Microglia Activation After Acute Muscle Trauma in Rats

Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation

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