[Study] Cannabinoids May Treat Neuropathic Symptoms and Neuroinflammatory Responses

What are Cannabinoids

Agonists of the CB2 receptor – such as cannabis-derived cannabinoids – may provide a treatment option for neuropathic symptoms and neuroinflammatory responses, according to a new study published by the European Journal of Neuroscience. The study was e-published ahead of print by the U.S. National Institute of Health.

“Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes”, states the study’s abstract. “In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord.”

With this in mind, researchers hypothesized that a CB2 agonist could “modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS [complex regional pain syndrome]by regulating CB2 and CX3CR1 signaling.”

Using chronic post-ischemia pain (CPIP) as a model of CRPS, researchers used rats to determine the potential benefits of a selective CB2 agonist meant to mimic the effects of cannabinoids.

Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking), whereas “intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP.”

MDA7 treatment was found to “interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP.”

The study concludes; “Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury.”

The full study can be found by clicking here.

Written by  on 

 

NOTE: Please remember to follow the laws of your state when it comes to your pharmaceutical care. Medical cannabis is not legal in all states in all forms, so be aware of what your state limitations are.

No Comments

Specific autoantibodies in patients with longstanding CRPS

Observe

We recently published a study on antibodies found in the blood of patients with longstanding Complex Regional Pain Syndrome [1].

Antibodies are substances produced by the body’s immune system. Their best-known role is to fight infection. However sometimes they go wrong, and bind to the body’s own cells, causing dysfunction or damage. These latter types of antibodies, which bind to body cells are termed autoantibodies.

Our recent study shows that most patients with longstanding CRPS have special types of autoantibodies in their blood. In contrast, these autoantibodies were not found in healthy volunteers, patients with fibromyalgia, neuropathic pain, or ‘myasthenia gravis’, an immune disease.

We already knew that special autoantibodies are produced by patients with recent onset CRPS [3][see Footnote]. Our new findings are relevant and important, because they demonstrate that autoantibodies are still being produced by people with CRPS as late as several years after injury, i.e. at a time when acute CRPS signs such as strong swelling and redness will have mellowed, and there is an expectation that the injury will have fully healed. The autoantibody presence in such longstanding CRPS shows that the patients’ immune systems remain abnormally activated.

The autoantibodies we identified were found to specifically activate the alpha1a receptor on cell surfaces. This particular receptor has previously been implicated in CRPS, and thus its activation might be relevant to the causes of CRPS. But there was something else – we initially thought that only those CRPS patients who responded to an immune treatment, intravenous immunoglobulin, would have autoantibodies, i.e. no more than 25% of all patients, see my Body in Mind blog August 2010. Yet, we found that, in fact a majority of all patients with longstanding CRPS had these specific autoantibodies in their blood. That meant that although only some patients with longstanding CRPS will respond to intravenous immunoglobulin a much larger group of of patients may have a specific immune dysregulation,.

How might these autoantibodies cause CRPS-related problems? Autoantibodies may bind either to nerve cells, or other cells situated close to nerves and may initiate abnormal sensory and/or motor nerve activation. An example of this type of autoantibody-nerve interaction is known as neuromyotonia, a neurological condition where different types of autoantibodies bind to peripheral motor nerves. The autoantibodies in neuromyotonia bind to the motor nerves and change ‘motor-nerve’ function, giving people abnormal muscle activations. It is thought that the autoantibodies in neuromyotonia may even cause (non-CRPS) neuropathic pain, which is a new field of research.

There are times where there is too much of a good thing, autoantibodies are one of those.
There are times where there is too much of a good thing, autoantibodies are one of those.

Having identified specific alpha 1a autoantibodies in patients’ blood, where do we go from here? We will look more closely at the CRPS immune dysregulation, and also investigate whether some immune procedures and drugs that work in other conditions can reduce CRPS pain. We have already conducted an audit [2], and have started a first trial to test this idea.

Our laboratory results on autoantibodies in longstanding CRPS are preliminary. We have yet to identify the molecular structure (i.e. the sequence of amino acids) against which these antibodies are directed – in fact our results suggest that the antibodies from different patients may bind to slightly different cell structures, having the common ultimate effect to activate alpha 1 receptors. We have also yet to develop a workable autoantibody blood test, as the test which we used is very cumbersome. Finally, but not least of all it will be important to convincingly show how these autoantibodies contribute to CRPS.

Nevertheless, I hope that these recent discoveries may eventually contribute to solve the riddle of what is causing CRPS after trauma, so that we can better treat those patients for whom currently no solution is available.

About Andreas Goebel

Andreas GoebelAndreas Goebel was born and raised in the Rhein/Main area in Southern Germany. He studied Medicine in Würzburg/Germany and started his training in Anaesthesiology and Pain Medicine at Würzburg Hospital; he also received a scholarship to study immunology at Harvard Medical School. Having returned to Germany things changed when Andreas met his Irish wife in the US and they ultimately decided to move to the UK. There, he continued his training, first attached to the Oxford rotation, then UCLH, and was appointed Consultant in Pain Medicine in 2007 at the Liverpool Walton Centre, the Country’s largest Pain Medicine department.

Andreas set up the first regional treatment network for Complex Regional Pain Syndrome, and also initiated and chaired the UK CRPS Guidance group, which published its comprehensive guidance in 2012). In 2008 he was appointed Assistant Professor (Senior Lecturer) in Pain Medicine at Liverpool University. Andreas’ chief research interest is in how the immune system, and specifically autoantibodies, may contribute to causing chronic pain and how this might translate into new treatments.

Bibliography

[1] Dubuis E, Thompson V, Leite MI, Blaes F, Maihofner C, Greensmith D, Vincent A, Shenker N, Kuttikat A, Leuwer M, Goebel A. Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. Pain 2014;155(11):2408-2417.

[2] Goebel A, Jones S, Oomman S, Callaghan T, Sprotte G. Treatment of long-standing complex regional pain syndrome with therapeutic plasma exchange: a preliminary case series of patients treated in 2008-2014. Pain Med 2014;15(12):2163-2164.

[3] Kohr D, Singh P, Tschernatsch M, Kaps M, Pouokam E, Diener M, Kummer W, Birklein F, Vincent A, Goebel A, Wallukat G, Blaes F. Autoimmunity against the beta(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain 2011;152(12):2690-2700.

Footnote

The autoantibodies identified in the acute setting included one type, antimuscarinic, which was likely also present in our samples, and another, anti-beta 2, which we did not detect. The laboratory method we used was different to that which was used to identify these acute-setting autoantibodies, however our method was sensitive to activating beta 2 antibodies, and thus should have picked them up had they been present in our samples. Their absence may be either due to geographically different patient populations (German vs. UK), the fact that the acute-setting tests used a immature cell type whereas we used adult cells, or because perhaps autoantibodies produced in the acute setting differ from those in the chronic setting. Of note, earlier investigations in the acute setting had not specifically looked for the new type of antibodies discovered now, so we don’t yet know whether these new antibodies are restricted to the chronic setting.

 

Originally posted on JULY 7, 2015 BY BIM 

No Comments

Complex Regional Pain Syndrome Diagnosis using the Budapest Criteria

PainScale

It is complex regional pain syndrome that brings many of us to this site. Many searching for some sort of way to explain where it comes from, what can be done to reverse it, what have medical professionals learned since we were diagnosed. Well medical professionals Konzelmann MDeriaz O, and Luthi F have come together to create an article on the success and utilization of a new diagnosing process. It is called the “Budapest Criteria” which is used to identify complex regional pain syndrome in its earlier stages.

Pain and How the Body Identifies It
Pain and How the Body Identifies It

How does this criteria help those with complex regional pain syndrome

With a successful process to diagnose patients, medical physicians might have a chance to catch patients earlier. And with a solid process this can be targeted and educated to those in the medical fields where doctors might see it most prevalent, emergency rooms and family physicians.

Who did their study focus on?

Their focus was on the partial form of complex regional pain syndrome type one (also known as reflexive sympathetic dystrophy). The specific target was those involving symptoms in only 1-3 fingers, a fairly uncommon occurrence with those with this condition. In the 5 years of their evaluating and observing patients in a rehabilitation ward their results had a fairly solid success rate. They applied this criteria to the evaluation of the radiological exams, the therapeutic results and vocational outcomes of the patients over time.

Of the 132 patients submitted with the diagnosis complex regional pain syndrome, only 16 were met the criteria where it effected only 1-3 fingers. Of these 16 people, 11 were men, 5 women with an average age of 43 years. While reviewing their progress, medical charts and success in therapy, 14 (88%) initially met the Budapest criteria and the other two were verified using a 3 phase bone scan. Now for the majority of the patients, only moderate improvement was made, and at the final follow-up, only 50% had returned to work.

PainScale
The current pain scale rating system used in the United States

What all did they review?

The physicians also compared against literature reviews, which had 19 cases eligible for comparisons. The largest differences is the increased number of male patients in this study, the later diagnosis, and a worse prognosis in the terms of return to work.

With this study and the literature already on file to review, the criteria’s success of diagnosis in 88% of the cases is a very good sign that there is a better chance on the horizon of catching new cases earlier. In turn allowing future patients a better chance of a normal and easier life with RSD than those already diagnosed. It also validated that the three-phase bone scan can only be used in doubtful cases in the first six months of the illness. And thought the partial formation of complex regional pain syndrome type 1 in the hand is rare and the prevalence being unknown. The long-term prognosis, (4 to 9 years) still suggest that earlier diagnosis is beneficial to patients abilities to returning to work.

How do I know this is information is true?

If you would like to read the full article, it can be found here: “Diagnosis of partial complex regional pain syndrome type 1 of the hand: retrospective study of 16 cases and literature review.” BMC Neurol. 2013 Mar 18;13:28. doi: 10.1186/1471-2377-13-28.

Where do I find more articles on complex regional pain syndrome?

More articles can be found at the National Institute of Health’s Library.

No Comments