Does Cannabinoids work for neuropathic pain?

Does Cannabinoids work for neuropathic pain? There is a relationship between diabetes, diabetic peripheral neuropathy (DPN) and neuropathic pain. But our understanding of underlying mechanisms leading to chronic pain in diabetes, remains poor.

  • “Recent evidence has demonstrated a prominent role of microglial cells in neuropathic pain states. One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoid receptors (CB) are expressed on neurons and microglia.”

101757290-Olegmalyshev-Dreamstime-INP-Instituut-voor-Neuropathische-Pijn dvn cannabisThese are the opening words of a brand-new article on “Cannabinoid mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain”, from the hand of Cory C Toth and colleagues. 

The authors point out that current treatments for neuropathic pain, have a focus on blocking neuro transmission. This, they say, may limit their effectiveness as the concomitant production of many inflammatory mediators continues to activate nociceptive neurons, contributing to pain hypersensitivity.[1]

They bring in mind that neuropathic pain promote the presence of inflammatory mediators within the spinal cord. This leads to a great variety of pro-inflammatory cytokines in the medula and the dorsal sensory ganglion. Such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα).

All these inflammatory enhancers are produced by non-neuronal cells, such as with glial cells. Thus, neuropathic pain currently is coined as gliopathic pain. 

Gliopathic pain 

Gliopathic pain, a new term! They follow their introduction stating that:

“One important microglial system is the family of cannabinoid (CB) receptors and its endogenous ligands. Endocannabinoids modulate microglial cell migration without disturbing their ability to phagocytose particles or produce nitric oxide

Although endocannabinoids, including anandamide and 2-arachidonoylglycerol (2-AG) act upon CB1 and CB2 receptors are secreted by neurons, they are more prominently produced in microglial cells during neuro inflammatory conditions.”

The authors studied clinically available drugs for neuropathic pain to detect their impact upon microglial activation in an animal model of chronic neuropathic pain. Mice receiving intranasal / intraperitoneal cannabidiol demonstrated lower densities of microglia in the dorsal spinal cord.

Diabetic mice receiving nabilone had amelioration of both tactile allodynia and thermal hyperalgesia. However, the authors did not identify any obvious differences in qualitative assessment of microglial activation. Nor differences in electron physiological detection of diabetic neuropathy.

So for the time being some biological readouts were positive, some effects were seen for Cannabinoids on the level of glia cells, but a crisp picture did not yet appear.

Jan M. Keppel Hesselink, MD, PhD, October 2010
‘Does cannabinoids work for neuropathic pain?’

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Referentielijst

[1] Toth CC, Jedrzejewski NM, Ellis CL, Frey WH 2nd. | Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. | Mol Pain. | 2010 Mar 17;6:16.


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