CRPS/RSD Drugs and Treatments
So far, 20 states have Medical Marijuana laws in place, with varying degrees of interference from the DEA. Those who have used it universally endorse its effectiveness for the worst symptoms of CRPS.
Another significant benefit to THC in the context of treating CRPS is that it acts synergistically with opioids, boosting their strength and even lessening the development of tolerance. This short section covers papers that address this phenomenon.
13. Antinociceptive Synergy between Δ9-Tetrahydrocannabinol and Opioids after Oral Administration
Recent news items about the benefits/dangers of using medical marijuana:
Striking a Nerve: Bungling the Cannabis Story an editorial by MedpageToday, one of the most authoritative sources of accurate medical information on the web, which shows the slanted coverage given stories of negative effects of cannabis.
Several drugs which are usually prescribed to treat osteoporosis have recently been used to treat CRPS. In addition to slowing or stopping bone demineralization and subsequent thinning and loss of bone density (osteopenia, osteoporosis), bisphosphonates apparently inhibit the release of inflammatory cytokines, which have been implicated as a mediator and propagator of CRPS pain.
1. Bisphosphonates: Focus on Inflammation and Bone Loss
Very recently, one of the bisphosphonates (neridronate) has shown powerful and unanticipated activity against CRPS1. This activity was observed in a small study (#13) last year, so this year a study involving 82 patients was carried out (#14), and one year following the study's end, no patient has any CRPS symptom of any kind.
Currently, a very large Phase III trial with neridronate is underway in the US. Not many details are currently known, but as of late July 2015 they were still looking for additional recruits for the study. See the first page in this site for the details and to see if you might qualify.
13. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study
Hyperbaric oxygen therapy (HBOT) involves breathing pure oxygen in a pressurized chamber or room. Conditions treated with hyperbaric oxygen therapy include serious infections, bubbles of air in your blood vessels (can happen during a scuba dive where ascent was too rapid, informally called "the bends"), and wounds that can't heal as a result of diabetes, radiation injury, or CRPS/RSD.
1. Hyperbaric oxygen therapy from the Mayo Clinic
Ketamine is a potent anesthetic with a history of abuse; it can induce psychotic states reminiscent of those seen with phencyclidine (PCP). In fact, the structures of the two molecules are extremely similar. It's also a powerful antagonist of the NMDA (N-Methyl-D-Aspartate) receptor with a likely role in the development of central sensitization. It is also, at this time, the most promising chemotherapeutic agent against CRPS/RSD that has yet been discovered, with the possible exception of the bis-phosphonates. However, we have far more experience with ketamine than with the other drug class.
1. Efficacy of Ketamine, esp. in cases of refractory CRPS
NOTE: There are dozens of articles on ketamine in the Library.
Note added 08/29/2013 - The journal CNS Neuroscience & Therapeutics devoted its June 2013 issue to review articles concerning research on ketamine; 10 of these articles are in the Library's Ketamine section.
Note added 10/03/2013 - I just ran across a paper called "Ketamine and Addiction", to which I want to call attention. The author attempts to make a case for the addiction liability of ketamine, based totally on anatomical features on brain fMRI. It's very revealing to see how a researcher can make a case for something, and actually get it accepted, without a single reference to a study involving humans becoming addicted to ketamine. Check it out - this is the kind of article that very good peer reviewing is supposed to reject; occasionally a study of questionable design is accepted.
Other drugs also exhibit similar antagonistic activity, and one has recently shown much promise as a new agent for CRPS. Called memantine (Namenda®), it shows the same NMDAR antagonism, but without the distressing side-effects, especially the psychological ones (dissociation, agitation, hallucinations). It's a drug that was developed (and is FDA-approved) for osteoporosis/osteopenia. Memantine's efficacy against CRPS was completely unanticipated, and, as so often happens in medicinal chemistry, was serendipitously observed in a population of osteoporosis patients who also happened to have CRPS. Here are but a few articles on this discovery:
There are many more articles (nearly 30) on ketamine and other NMDAR antagonists in the Library.
Methadone, a staple of opioids used for chronic pain, including CRPS, is subject to highly variable metabolism rates due to enzyme mixtures, which are genetically determined and unique to each person and can cause problems with compliance urinalyses. Based on the number of receptor sites expressed, a person falls into one of four categories, from "slow metabolizer" to "ultra-fast metabolizer". Those in the "slow" category might take several days to show no methadone, while the "ultra-fast" folks (like me) can take a 10mg tablet of methadone, and, an hour later, show no trace of the drug in the urine.
Genetic screening can tell, quickly and cheaply, into which category you fall. If you take methadone, I strongly urge you to do this. If you happen to be in the ultra-fast category, you'll want to be able to document this for any pain management physician who uses urinalysis to verify that you're taking the prescribed drugs (instead of selling them or something equally illegal). In fact, I did the research and got the test after I'd showed up with clean urine for three docs in a row. I guarantee that knowing my status beforehand would have simplified my life greatly at those times!
1. Methadone-Drug Interactions
Mirror therapy began with phantom limb Tx, where a box with a mirror bisecting it within allowed the patient to "see" two arms when only one is there. This has been extended to CRPS treatment.
1. Mirror Visual Feedback Therapy and Its Application for the Tx of CRPS
Many years ago, cutting the nerve(s) seemed to make sense, but it's mostly been replaced with more reversible and selective techniques. Still, sympathectomies have their supporters in the medical community, as well as serious detractors.
1. Evidence-Based Interventional Pain Medicine 16. CRPS
Oxymorphone is much stronger than oxycodone; patients must be very careful to avoid overdosing and/or interactions with other opioids or sedatives, tranquilizers, hypnotics, etc.
Tolerance, compliance, abuse, addiction, withdrawal, etc.
1. A Clinical Guide to Opioid Analgesia; 135 pages
In 2012, the journal Pain Physician devoted an entire issue to opioids and their use. All 19 chapters are now available here:
NOTE: There are dozens of articles on opioids in the Library.
The first comprehensive, evidence-based clinical practice guideline to assist clinicians in prescribing potent opioid pain medications for patients with chronic non-cancer pain. Published in three sequential papers (#1, 2, & 3).
Involves therapist-controlled physical therapy with no "RSD drugs" and in which patient expressions of pain (verbal or nonverbal) are ignored. Definitely controversial (at least in the US), but it's getting results even for long-term CRPS patients whose disease has progressed very far.
1. Pain exposure physical therapy may be a safe and effective treatment for longstanding CRPS 1: a case series
1. Calmare Pain Therapy Treatment
Following the success of spinal cord stimulation (SCS), additional methods for neural stimulation have been investigated, and include a variety of approaches. The most exciting and potentially revolutionary route, currently, is direct brain stimulation, using either electrical or magnetic energy to affect the brain's nerve cells.
1. Computer-based model of epidural motor cortex stimulation: Effects of electrode position and geometry on activation of cortical neurons
Highly variable results, very dependent on practitioner skill. There are side effects that are serious for some, but for others, it's been a real miracle.
1. Report from National Health and Clinical Excellence; 36 pages
NOTE: There are 14 articles on SCS in the Library
Systemic toxic reactions to LAs can result from high blood levels of the drug due to accidental intravenous (IV) infusion. This section covers the many types of neural blocks done in treating CRPS.
Palmitoylethanolamide (PEA) is an endogenous (occurs naturally in the body) compound in a class called lipid mediators, and is known to exert antinociceptive effects, as well as prevent neurotoxicity and neurodegeneration. It also inhibits peripheral inflammation and mast cell degeneration, and can modulate microphage response. It does this by activating a special receptor called PPAR-α.
1. Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism
Not a concern as much as an unknown analgesic agent with proven efficacy.
Vitamin C has been utilized in a number of strategies to avoid the development of CRPS following (and occasionally before) an event known to cause CRPS in some individuals. The two most common causes of CRPS, respectively, are surgery and fractures.
1. Efficacy and Safety of High-dose Vitamin C on Complex Regional Pain Syndrome in Extremity Trauma and Surgery - Systematic Review and Meta-Analysis
The phrase "Complementary and Alternative Medicine" (CAM) is most commonly associated with therapeutic techniques or treatments that are outside the realm of typical Western medicine, although they might be used in other countries for medical applications. Some CAM techniques have histories stretching back many thousands of years, such as massage therapy, herbs, and acupuncture.
In the early 1990s, the National Center for Complementary and Alternative Medicine (NCCAM) was founded as part of the National Institutes of Health (NIH). According to its web site, "NCCAM is dedicated to exploring complementary and alternative healing practices in the context of rigorous science, training complementary and alternative medicine (CAM) researchers, and disseminating authoritative information to the public and professionals."
Intrathecal delivery of medications involves the direct introduction of drugs into the spinal column, i.e., the cerebrospinal fluid (CSF). Although obviously quite invasive, the technique embodies several important advantages, especially for those who are running out of options to achieve satisfactory pain control:
Most narcotics can be introduced intrathecally, but many are being developed specifically for this application. Recently, the first drug was approved by the FDA specifically for chronic neuropathic pain, called Prialt® (ziconotide), which was first isolated from the toxins that a small Ecuadorean tree frog secretes from its skin to avoid being eaten.
1. Administering Ziconotide and Monitoring Patients Treated with Ziconotide: Expert Opinions