Capsaicin, derived from hot chili pepper plants, has been used to treat various types of pain, and a high concentration capsaicin patch (HCCP) is approved for the treatment of neuropathic pain. In a real-world study published in Pain Practice that included 97 outpatients in Germany diagnosed primarily with neuropathic back pain, postoperative/posttraumatic neuropathic pain, or postherpetic neuralgia (shingles pain), patients appeared to benefit from multiple HCCP applications.
Among the study participants, 38 received 2 HCCP treatments, and 59 received at least 3. Following HCCP treatments, most patients required significantly lower doses of opioids to manage their pain. Also, two-thirds of patients experienced a reduction in pain intensity after multiple HCCP treatments, and the proportion of patients experiencing a reduction in pain intensity was substantially higher among those who received at least 3 applications compared with those who received 2 applications.
“Consistent with the progressive response seen in prospective clinical trials involving repeated use of topical capsaicin, our research indicates that patients appear to benefit from multiple applications in terms of pain intensity and concomitant opioid use in real-world clinical practice,” said corresponding author Kai-Uwe Kern, MD, PhD, of the Institute for Pain Medicine/Pain Practice, in Wiesbaden, Germany.
The links between alcohol and pain are complex. Research published in theBritish Journal of Pharmacology suggests that chronic alcohol consumption may increase drinkers’ pain sensitivity through two different molecular mechanisms – the first driven by alcohol intake and the second by alcohol withdrawal.
The researchalso suggests potential new drug targets for treating alcohol-associated chronic pain and hypersensitivity.
“There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence,” says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine, and a professor of neuroscience at Scripps Research. “Pain is both a widespread symptom in patients suffering from alcohol dependence, as well as a reason why people are driven to drink again.”
Over time, alcohol use disorder (AUD) can trigger the development of numerous chronic diseases, including heart disease, stroke, liver disease and some cancers. Among the many impacts of long-term alcohol consumption is pain: more than half of people with AUD experience persistent pain of some type. This includes alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms.
Studies have also found that AUD is associated with changes in how the brain processes pain signals, as well as changes to how immune system activation occurs. In turn, this pain can lead to increased alcohol consumption. Moreover, during withdrawal, people with AUD can experience allodynia, in which a harmless stimulus is perceived as painful.
Roberto and her colleagues were interested in learning the underlying causes of these different types of alcohol-related pain. In the new study, they compared three groups of adult mice: animals that were dependent on alcohol (excessive drinkers), animals that had limited access to alcohol and were not considered dependent (moderate drinkers), and those that had never been given alcohol.
In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity. Separately, about half of the mice that were not dependent on alcohol also showed signs of increased pain sensitivity during alcohol withdrawal but, unlike the dependent mice, this neuropathy was not reversed by re-exposure to alcohol.
When Roberto’s group then measured levels of inflammatory proteins in the animals, they discovered that while inflammation pathways were elevated in both dependent and non-dependent animals, specific molecules were only increased in dependent mice. This indicates that different molecular mechanisms may drive the two types of pain. It also suggests which inflammatory proteins may be useful as drug targets to combat alcohol-related pain.
“These two types of pain vary greatly, which is why it is important to be able to distinguish between them and develop different ways to treat each type,” says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.
Roberto’s group is continuing studies on how these molecules might be used to diagnose or treat alcohol-related chronic pain conditions.
“Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies,” says co-senior author Nicoletta Galeotti, PhD, associate professor of preclinical pharmacology at the University of Florence.
Cannabis’s pain reduction effects appear to be less effective than previously though. Photo by Kindel Media
Cannabis product use provides modest, short-term improvements in chronic pain, albeit with some side effects, according to a large review of research on cannabis pain management. The review also revealed a general lack of high quality evidence such as randomised controlled trials (RCTs). The data will be uploaded to a web app made by Oregon Health & Science University to inform clinicians on cannabis medications.
Reporting in Annals of Internal Medicine, researchers found evidence to support a short-term benefit in treating neuropathic pain with two synthetic products with 100% tetrahydrocannabinol (THC): dronabinol (under the trade name Marinol) and nabilone (Cesamet). Another product, a sublingual spray of equal parts THC and cannabidiol (CBD), known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain. All of the products had side effects, such as nausea, sedation and dizziness.
From 3000 studies, the researchers selected RCTs or comparative observational studies of patients with chronic pain that compared cannabis products with a placebo or no treatment (that is, usual care) for at least 4 weeks of treatment or follow-up.
They ended up with a total of 25 with scientifically valid evidence – 18 RCTs and seven observational studies. Cannabinoids were categorised as high, comparable, or low THC-to-CBD ratio. The researchers found:
Synthetic products with high THC (> 98%) and little or no CBD: moderate improvement in pain, but greater sedation risk and possible increase in dizziness
Extracted products with majority THC (THC:CBD ratio ranging from 3:1 to 47:1): no significant improvement in pain, but greater study withdrawal because of adverse events and dizziness
Sublingual sprays with comparable THC and CBD levels: small improvement in pain but a much greater increased risk of dizziness and sedation and a moderate increase in nausea
Besides these findings, there was little evidence to support any other conclusions.
“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, PharmD, emeritus professor at OHSU. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.
“Unfortunately, there is very little scientifically valid research into most these products. We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”
“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors noted.
This situation makes it difficult to guide patients.
“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, MD. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”
The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes ‘clinician briefs’ to help health care workers translate the clinical implications.
“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, MD, MCR, professor of medicine at OHSU.
