Category Archives: Neuropathic Pain
Antihyperalgesic Activities of Endocannabinoids in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.
“Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of the antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). However, their use is sometimes limited by the development of a painful sensory neuropathy, which does not respond well to drugs.
Smoked cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy.
The aim of this study was to evaluate whether the expression of endocannabinoid system molecules is altered during NRTI-induced painful neuropathy, and also whether endocannabinoids can attenuate NRTI-induced painful neuropathy.
Conclusion: These data show that ddC induces thermal hyperalgesia, which is associated with dysregulation of the mRNA expression of some endocannabinoid system molecules. The endocannabinoids AEA and 2-AG have antihyperalgesic activity, which is dependent on cannabinoid receptor and GPR55 activation. Thus, agonists of cannabinoid receptors and GPR55 could be useful therapeutic agents for the management of NRTI-induced painful sensory neuropathy.”
[Role of cannabinoid receptor 1-mediated synaptic plasticity in neuropathic pain and associated depression].
“Neuropathic pain is a class of pain caused by an injury or diseases of the somatosensory system and characterized by spontaneous pain, allodynia, and hyperalgesia. It is well established that central sensitization is one of the key mechanisms underlying the development and maintenance of neuropathic pain. Cannabinoid receptor 1 (CB1R) of endocannabinoid system modulates synaptic transmission, regulates synaptic plasticity, inhibits central sensitization, and thus attenuates neuropathic pain. Recent studies have shown that activation of CB1R also involves in the relief of neuropathic pain-induced depression.” https://www.ncbi.nlm.nih.gov/pubmed/28364110
Cannabis Reduces Opioid Dose in the Treatment of Chronic Non-Cancer Pain
“Cannabinoids block pain responses in virtually every laboratory pain model tested.
In models of acute or physiological pain, cannabinoids are highly effective against thermal, mechanical, and chemical pain, and are comparable to opioids in potency and efficacy.1 In models of chronic pain, cannabinoids exhibit efficacy in the modulation of both inflammatory2 and neuropathic pain.3
Recent reviews describe an endogenous cannabinoid system involved in pain modulation that produces analgesia through the same brainstem circuitry involved in opioid analgesia.1., 4., 5., 6. Although co-administration of Δ-9-tetrahydrocannabinol (THC) with μ opioid agonists can potentiate the antinociceptive effects of each agent, an opioid is not required for cannabinoid analgesia.5., 6. Co-administration of a cannabinoid may lead to a lower opioid requirement. In an N-of-1 trial, oral THC reduced the pain of familial Mediterranean fever such that the use of breakthrough opioid for pain relief decreased significantly.7
Recently, in Canada, the Medical Marijuana Access Program allows patients to apply to Health Canada for access to dried cannabis for medicinal purposes. Although smoked cannabis is not an ideal delivery system, it is efficient and results in plasma concentration curves parallel to those seen after intravenous administration.8 We present three patients who used small doses of smoked marijuana in combination with an opioid.
These cases are consistent with preclinical work demonstrating that cannabinoids exhibit analgesic effects and may potentiate the antinociceptive effects of opioids. These patients were able to decrease the dose of opioid by 60–100% as compared to before the regular use of smoked marijuana. With the introduction of smoked marijuana, each patient reported better pain control.
Unfortunately, the source of smoked marijuana used by patients, and the percentage of THC in it, is unknown. All patients reported previous exposure to cannabis at some time in their lives before the onset of their pain, and the relevance of this experience also is unknown. Standardized measures of pain were not used, and the information presented was based on the patients’ verbal report when they presented for follow-up appointments at the Pain Management Unit. Nonetheless, these cases suggest that further research regarding the role of cannabinoids as analgesics and the combination of cannabinoids with opioids in the control of pain is needed.”
http://www.jpsmjournal.com/article/S0885-3924(03)00142-8/fulltext
Allodynia Lowering Induced by Cannabinoids and Endocannabinoids (ALICE).
“Neuropathic pain is a neurological disorder that strongly affects the quality of life of patients. The molecular and cellular mechanisms at the basis of the neuropathic pain establishment still need to be clarified. Among the neuromodulators involved in the pathological pain pathways, endocannabinoid system could be deeply involved in both neuronal and non-neuronal mechanisms responsible for the appearance of tactile allodynia. Indeed, the function and dysfunction of this complex system in the molecular and cellular mechanisms of chronic pain induction and maintenance has been widely studied over the last two decades. In this review article, we highlighted the possible modulation of the endocannabinoid system in the neuronal, glial and microglial modulation in neuropathic pain treatment.”
Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.
“Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting.
The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone.
Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids.
Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions.
As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.”
Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-Tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis
“The aim of the present study was to evaluate the efficacy of an oral formulation of Δ9-tetrahydrocannabinol (ECP002A) in patients with progressive multiple sclerosis (MS).
Pain was significantly reduced when measured directly after administration of ECP002A in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo. Cognitive testing indicated that there was no decline in cognition after 2 or 4 weeks of treatment attributable to ECP002A compared with placebo.
Implications This study specifically underlines the added value of thorough investigation of pharmacokinetic and pharmacodynamic associations in the target population. Despite the complex interplay of psychoactive effects and analgesia, the current oral formulation of Δ9-tetrahydrocannabinol may play a role in the treatment of spasticity and pain associated with MS because it was well tolerated and had a stable pharmacokinetic profile.”
The use of cannabinoids (CBs) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN): A retrospective review.
“CIPN is a common toxicity associated with the use of chemotherapy (CT) agents such as platinums, taxanes and vinca alkaloids. Patients (pts) may suffer from pain that adversely affects their quality of life, regardless of their disease trajectory.
Preclinical research has shown CBs to be effective in preventing CIPN.
CBs can be beneficial for cancer pain, although their specific benefit in pts with CIPN remains unknown.
Treatment with CBs appears to benefit some pts with CIPN.
Further research is needed to explore the optimal use of CBs in pts with CIPN.”
Cannabinoid Buccal Spray for Chronic Non-Cancer or Neuropathic Pain: A Review of Clinical Effectiveness, Safety, and Guidelines [Internet].
“Chronic pain is a complex, severe and debilitating condition which can lead to a considerable reduction in function and quality of life. Patients may present with different forms of chronic pain resulting from a number of identifiable causes, including pain due to lesion or dysfunction of the nerves, spinal cord or brain (neuropathic pain), or persistent pain caused by other non-malignant conditions, such as low-back pain or pain due to inflammation of various arthritic conditions. The prevalence of chronic non-cancer pain or neuropathic pain among Canadian adults is not well known. However, prevalence estimates using large, population-based questionnaires have shown that 4% to 8% of the general population in the developed world experiences neuropathic pain, suggesting that approximately two million Canadians may be affected by this disabling condition. Chronic pain is of particular concern among Canadians aged 65 years and older; based on cross-sectional data from the 1996/1997 National Population Health Survey and the 2005 Canadian Community Health Survey, chronic pain was estimated to affect 27% and 38% of seniors living in households and health care institutions, respectively. A number of treatments are available for the management of neuropathic pain or chronic non-cancer pain. These include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine), anticonvulsants (pregabalin, gabapentin, carbamazepine, phenytoin), topical lidocaine, and opioid analgesics. However, these medications are associated with limited pain relief and numerous adverse effects. The therapeutic use of several synthetic cannabinoid products for the symptomatic relief of chronic pain has also been studied. In particular, a combination of two products, delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) marketed under the name Sativex® is available for use as a buccal spray. This cannabis-based agent is approved for use in Canada as an add-on therapy for adult patients experiencing muscle spasticity caused by multiple sclerosis (MS), and it has received a Notice of Compliance with conditions for MS-related central neuropathic pain and the treatment of cancer pain unresponsive to opioids. The purpose of this review is to examine the available published literature relating to THC:CBD buccal spray for the treatment of chronic non-cancer or neuropathic pain in adults.”
The Role of Cannabinoid Receptors in the Descending Modulation of Pain.
“The endogenous antinociceptive descending pathway represents a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes the periaqueductal grey (PAG)-rostral ventromedial medulla (RVM)-dorsal horn (DH) axis, which is the best characterized pain modulation system through which pain is endogenously inhibited. Thus, an alternative rational strategy for silencing pain is the activation of this anatomical substrate.
Evidence of the involvement of cannabinoid receptors (CB) in the supraspinal modulation of pain can be found in several studies in which intra-cerebral microinjections of cannabinoid ligands or positive modulators have proved to be analgesic in different pain models, whereas cannabinoid receptor antagonists or antisense nucleotides towards CB1 receptors have facilitated pain.
Like opioids, cannabinoids produce centrally-mediated analgesia by activating a descending pathway which includes PAG and its projection to downstream RVM neurons, which in turn send inhibitory projections to the dorsal horn of the spinal cord.
Indeed, several studies underline a supraspinal regulation of cannabinoids on g-aminobutyric acid (GABA) and glutamate release which inhibit and enhance the antinociceptive descending pathway, respectively. Cannabinoid receptor activation expressed on presynaptic GABAergic terminals reduces the probability of neurotransmitter release thus dis-inhibiting the PAG-RVM-dorsal horn antinociceptive pathway.
Cannabinoids seem to increase glutamate release (maybe as consequence of GABA decrease) and to require glutamate receptor activation to induce antinociception. The consequent outcome is behavioral analgesia, which is reproduced in several pain conditions, from acute to chronic pain models such as inflammatory and neuropathic pain.
Taken together these findings would suggest that supraspinal cannabinoid receptors have broad applications, from pain control to closely related central nervous system diseases such as anxiety and depression.”