Role of CB2 in complex regional pain syndrome

Role of CB2 in complex regional pain syndrome

Cannabinoids May Treat Neuropathic Syndromes & Neuroinflammatory Responses

Complex Regional Pain Syndrome (CRPS) is a neurological disorder previously referred to as "reflex sympathetic dystrophy". Patients with CRPS experience chronic pain in a certain part of their body. The pain can start after a minor sprain or after just having surgery. But which appears much more serious than one would expect considering the original injury. The cannabinoid receptor 2 (CB2) has emerged as a promising target for the treatment of various neuropathic pain syndromes such as CRPS


Complex regional pain syndrome (CRPS)

All patients with CRPS experience chronic pain in some part of their body. Most of the time the pain is in an arm or a leg. Additionally, they will also have some of the following symptoms:

Rehabilitation for Complex Regional Pain Syndrome Type I
  • A difference in temperature or color of the skin of the affected limb
  • Limits in the range of motion of the limb
  • Very sensitive skin, similar to a painful sunburn
  • Excessive sweating in the affected limb
  • Edema of a hand or foot
  • Tremors
  • Weakness in one arm or one leg
  • Changes in skin, hair or nails on the affected side
  • Decreased bone density (and possible fractures)
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MDA7, a new CB2 agonist

according to a new study published by European Journal of Neuroscience, CB2 receptor agonists - such as cannabinoids derived from cannabis - may offer treatment for neuropathic symptoms and neuroinflammatory responses. The study was published in advance by the United States National Institute of Health.

figure-3-involvement-the-cb-2-r-in-the-pain-in-response-has-a-cutaneous lesion-les copy
Involvement of CB 2 R in pain. Here in response to a skin lesion, activating in part the keratinocytes that secrete neuropeptides

The study focuses on models of neuropathic pain, on activated microglia expressing the CB2 receptors that are observed in the spinal cord. Using chronic post-ischemic pain (CPIP) as a model of CRPS [Complex Regional Pain Syndrome] the researchers used rats to determine the potential benefits of a selective CB2 agonist intended to mimic the effects of cannabinoids.

Role of microglial cells in the inflammatory response

With this in mind, the researchers hypothesized that a CB2 agonist could "modulate neuroinflammation and neuropathic pain in a model of ischemia of CRPS by regulating CB2 and CX3CR1 signaling."

Rats in the CPIP group exhibited significant hyperemia (abnormal increase in blood flow to an organ) and edema of the hind paw, spontaneous pain behaviors (trembling and licking of the hind paw), while administration intraperitoneally (in the spinal cord) of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by pain CPIP. Allodynia is the occurrence of pain triggered by a stimulus that is normally painless.

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Allodynia and hyperalgesia during neuropathic pain


Treatment with MDA7 interferes with early events in the neuropsychological response. This by suppressing peripheral edema, spinal microglial activation, and expression of CX3CR1 and CB2 receptors on microglia in the spinal cord. MDA7 also attenuated the loss of intraepidermal nerve fibers induced by CPIP.

The study concludes; “Our results suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for the treatment of neuropathic and neuro-inflammatory symptoms induced by CRPS-I in the setting of ischemia and reperfusion injury. "

The major agonists of CB1 & CB2 receptors, the cannabinoids present in the cannabis plant

MDA7, this new agonist of the CB2 receptor like all cannabinoids binds to the CB2 receptor (mainly THC). It may offer a therapeutic approach for neuropathic and neuroinflammatory symptoms induced by complex regional pain syndrome. But also, MDA7 is effective especially in the context of a decrease in the arterial blood supply to an organ (ischemia), and in the case of a restoration of the blood circulation ofa blocked artery (reperfusion of wounds).

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