“A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (ie, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that ‘medicinal’ cannabis or cannabinoid-based medications relieve pain in human diseases, such as cancer, multiple sclerosis, and fibromyalgia. Here, we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.” https://www.ncbi.nlm.nih.gov/pubmed/28857069 https://www.nature.com/npp/journal/vaop/naam/abs/npp2017204a.html]]>
Category Archives: Chronic Pain
Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli.
“The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain.
However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo.
These results provide evidence that endocannabinoids can have opposing effects on nociceptive vs. non-nociceptive pathways and suggest that cannabinoid-based therapies may be more appropriate for treating pain disorders in which hyperalgesia and not allodynia is the primary symptom.”
Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation.
“This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders.
It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings.
These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF-induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects.SIGNIFICANCE:
Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a novel approach to provide analgesic relief without central side effects.” https://www.ncbi.nlm.nih.gov/pubmed/28722246 http://onlinelibrary.wiley.com/doi/10.1002/ejp.1085/abstract]]>Antinociceptive effects of HUF-101, a fluorinated cannabidiol derivative.
“Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use. Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects. These findings show that HUF-101 produced antinociceptive effects at lower doses than CBD, indicating that the addition of fluoride improved its pharmacological profile. Furthermore, some of the antinociceptive effects of CBD and HUF-101 effects seem to involve the activation of CB1 and CB2 receptors.” https://www.ncbi.nlm.nih.gov/pubmed/28720466 http://www.sciencedirect.com/science/article/pii/S0278584617302233]]>
Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.
“Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient and tolerable for chronic pain relief. When reported, adverse effects related to these CAM were minor.” https://www.ncbi.nlm.nih.gov/pubmed/28669581
“To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain.
Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC.”