Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain.

Posted on May 10, 2015 by David

“Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN) and neuropathic pain (NeP), our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor.

Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states.

One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoidreceptors (CB) are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ)-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state.

The prevention of microglial accumulation and activation in the dorsal spinal cord was associated with limited development of a neuropathic pain state.

Cannabinoids demonstrated antinociceptive effects in this mouse model of DPN.

These results suggest that such interventions may also benefit humans with DPN, and their early introduction may also modify the development of the NeP state.” http://www.ncbi.nlm.nih.gov/pubmed/20236533

“Tetrahydrocannabinol (THC), a component in marijuana, acts at both CB1 and CB2 receptors, but other forms of cannabinoids such as cannabinol and cannabidiol act predominantly at CB2 receptors. Such CB2 agonists may be potential anti-inflammatory therapies, antagonizing the 2-AG-induced recruitment of microglia and impacting upon development of an inflammatory state. Such properties may permit the cannabinoids to act in the prevention of microglial activation, perhaps limiting the development of neuropathic pain.

The present data confirm the efficacy of cannabinoid agonists, both for the CB1 and CB2 receptor, in modulation of acute thermal and tactile hypersensitivity as features of neuropathic pain. Furthermore, CB1 agonism from the onset of the offending stimulus (diabetes) normally leading to neuropathic pain ameliorated the development of a neuropathic pain state.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845559/

http://www.thctotalhealthcare.com/category/neuropathic-pain/

CB1 Knockout Mice Unveil Sustained CB2-Mediated Anti-Allodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.

Posted on April 24, 2015 by David

“Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors. However, unwanted CB1-mediated cannabimimetic effects limit clinical use…

Our results using the mixed CB1/CB2 agonist document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain.

Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1receptor activation.”

http://www.ncbi.nlm.nih.gov/pubmed/25904556

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Intrathecal Injection of JWH-015 Attenuates Bone Cancer Pain Via Time-Dependent Modification of Pro-inflammatory Cytokines Expression and Astrocytes Activity in Spinal Cord.

Posted on April 22, 2015 by David

“Cannabinoid receptor type 2 (CB2) agonists display potential analgesic effects in acute and neuropathic pain.

Overall, our results provided evidences for the persistent participation of inflammation reaction in the progression of bone cancer pain, and demonstrated that JWH-015 reduced the expression of IL-1β, IL-6, IL-18, and TNF-α and inhibited astrocytes activation in a time-dependent manner, thereby displaying an analgesic effect.”

http://www.ncbi.nlm.nih.gov/pubmed/25896633

http://www.thctotalhealthcare.com/category/bone-cancer-2/

CB1 receptors modulate affective behaviour induced by neuropathic pain.

Posted on April 12, 2015 by David

“Patients suffering from chronic pain are often also diagnosed with a psychiatric condition, in particular generalized anxiety and major depression. The underlying pathomechanisms contributing to this comorbidity, however, are not entirely clear.

In this manuscript we have focussed on the potential role of the cannabinoid receptor CB1, because it is known to modulate neuronal circuits contributing to chronic pain states and affective behaviours.

For this purpose we analysed the consequences of a partial sciatic nerve ligation on anxiety- and depression related behaviours in mice lacking CB1 receptors.

Our results show that the development of mechanical hypersensitivity was similar in CB1 deficient mice and wild type controls. However, CB1 knockouts showed much more pronounced behavioural manifestations of anxiety-related behaviors in the light-dark and zero-maze tests, sucrose anhedonia, and disturbed home-cage activity.

These results indicate that the endocannabinoid system affects chronic pain-induced mood changes through CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/25863168

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy.

Posted on April 7, 2015 by David

“A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis.

In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis…

This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated a dose dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain.

This adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25843054

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy.

Posted on February 27, 2015 by David

“The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist…

Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25712641

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Are Cannabinoids Effective for Orofacial Pain States?

Posted on February 27, 2015 by David

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

http://www.thctotalhealthcare.com/category/pain-2/

The Effectiveness of Cannabinoids in the Management of Chronic Nonmalignant Neuropathic Pain: A Systematic Review.

Posted on January 31, 2015 by David

“… a systematic review to assess the effectiveness of cannabis extracts and cannabinoids in the management of chronic nonmalignant neuropathic pain…

Randomized placebo-controlled trials (RCTs) involving cannabis and cannabinoids for the treatment of chronic nonmalignant pain were selected…

Evaluation of these studies suggested that cannabinoids may provide effective analgesia in chronic neuropathic pain conditions that are refractory to other treatments.

Conclusion: Cannabis based medicinal extracts used in different populations of chronic nonmalignant neuropathic pain patients may provide effective analgesia in conditions that are refractory to other treatments. ”

http://www.ncbi.nlm.nih.gov/pubmed/25635955

http://www.thctotalhealthcare.com/category/neuropathic-pain/

A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.

Posted on October 2, 2014 by David

“Peripheral neuropathic pain (PNP) poses a significant clinical challenge.

The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated…

THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use.

In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.”

http://www.ncbi.nlm.nih.gov/pubmed/25270679

http://www.thctotalhealthcare.com/category/neuropathic-pain/

Cannabinoids for Neuropathic Pain.

Posted on August 28, 2014 by David

“Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects.

The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis.

Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions.

This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25160710

http://www.thctotalhealthcare.com/category/neuropathic-pain/