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/

Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.

Posted on April 27, 2015 by David

“Cannabis has been used for thousands of years as a therapeutic agent for pain relief, as well as for recreational purposes.

Delta-9-Tetrahydrocannabinol (Δ9-THC)… produces antinociceptive effects in a wide range of preclinical assays of pain.

Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids.

Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC.

These results suggest that various constituents of this plant may interact in a complex manner to modulate pain.

The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model…

Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching.

These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.

The results obtained in the present study are consistent with the view that Δ9-THC is the major phytocannabinoid present in marijuana that produces antinociception in the acetic acid abdominal stretching test.

…these results suggest that there is potential to develop medications containing various concentrations of specific phytocannabinoids to optimize therapeutic effects (e.g., antinociception) and minimize psychomimetic effects.

In sum, the results of the present study further support the notion that Δ9-THC is the predominant constituent of marijuana that is responsible for eliciting antinociceptive effects and indicate that CB1 receptors play a predominant role in mediating these effects.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765124/

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

Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats.

Posted on April 12, 2015 by David

“The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones…

These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones.”

http://www.ncbi.nlm.nih.gov/pubmed/25863271

Endocannabinoids and acute pain after total knee arthroplasty.

Posted on January 22, 2015 by David

“Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain.

The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA…

Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint.”

http://www.ncbi.nlm.nih.gov/pubmed/25599456

The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat.

Posted on December 3, 2014 by David

“Our study addressed the hypothesis that spinal release of endogenous opioids underlies Delta9-tetrahydrocannabinol (Delta9-THC)-induced antinociception in Freund’s adjuvant-induced arthritic and nonarthritic rats…

Our results indicate that morphine or Delta9-THC is equally potent and efficacious in both nonarthritic and arthritic rats.

Delta9-THC-induced antinociception…

We hypothesize that the elevated idyn A level in arthritic rats contributes to hyperalgesia by interaction with N-methyl-D-aspartate receptors, and that Delta9-THC induces antinociception by decreasing idyn A release.”

http://www.ncbi.nlm.nih.gov/pubmed/15189765

http://www.thctotalhealthcare.com/category/arthritis/

The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor.

Posted on December 3, 2014 by David

“Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain.

We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats.

The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was determined…

Our results indicate that the cannabinoid CB(2) receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17588560

http://www.thctotalhealthcare.com/category/arthritis/

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

Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

Posted on December 3, 2014 by David

“Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail…

This study suggests that THC could be a future pharmacological option in the treatment of muscle pain.

The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25446925

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

Impact of efficacy at the mu opioid receptor on antinociceptive effects of combinations of mu opioid receptor agonists and cannabinoid receptor agonists.

Posted on September 11, 2014 by David

“Cannabinoid receptor agonists, such as delta-9-tetrahydrocannabinol (Δ9-THC), have antinociceptive effects and, are increasingly used to treat pain, and medications including cannabinoid receptor agonists are approved for use in humans.

Cannabinoid receptor agonists [e.g. Δ9-tetrahydrocannabinol (Δ9-THC)] enhance the antinociceptive effects of mu opioid receptor agonists, suggesting that combining cannabinoids with opioids would improve pain treatment.

…these results provide additional support for combining opioids with cannabinoids to treat pain.”

http://jpet.aspetjournals.org/content/early/2014/09/05/jpet.114.216648.long

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

Treatment with a Heme Oxygenase 1 Inducer Enhances the Antinociceptive Effects of µ-Opioid, δ-Opioid, and Cannabinoid 2 Receptors during Inflammatory Pain.

Posted on September 11, 2014 by David

“The administration of µ-opioid receptor (MOR), δ-opioid receptor (DOR), and cannabinoid 2 receptor (CB2R) agonists attenuates inflammatory pain.

We investigated whether treatment with the heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the local effects and expression of MOR, DOR, or CB2R during chronic inflammatory pain…

This study shows that the HO-1 inducer (CoPP) increased the local antinociceptive effects of MOR, DOR, and CB2R agonists during inflammatory pain by altering the peripheral expression of MOR and DOR.

Therefore, the coadministration of CoPP with local morphine, DPDPE, or JWH-015 may be a good strategy for the management of chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25204546

Cannabinoid Receptor Type 1 Antagonist, AM251, Attenuates Mechanical Allodynia and Thermal Hyperalgesia after Burn Injury.

Posted on September 5, 2014 by David

“Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. This study tested the hypothesis that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain.

CONCLUSIONS::

AM251 inhibited nociceptive behaviors after burn even beyond 7-day period of administration. Although many studies have documented the utility of CB1R agonists, this study indicates that endogenous cannabinoids may have an unexpected pronociceptive effect during development of burn pain, explaining why CB1R antagonist, AM251, improves nociceptive behaviors.”

http://www.ncbi.nlm.nih.gov/pubmed/25188001