Cannabis for the Treatment of Chronic Pain in the Era of an Opioid Epidemic: A Symposium-Based Review of Sociomedical Science.

OBJECTIVE: This manuscript reviews medical literature published pertaining to the management of chronic pain with medical marijuana therapy (MMJ), with an emphasis on the social, medical, and legal aspects of therapy. DESIGN: Narrative review of peer-reviewed literature. METHODS: The 3rd Symposium on Controlled Substances and Their Alternatives for the Treatment of Pain was held in Boston on February 27, 2016, with a focus on MMJ for the treatment of chronic pain. Invited speakers had diverse backgrounds, including pain management, addiction psychiatry, neurology, and legal authorities. The purpose of this conference and this subsequent narrative review is to provide a medical, legal, and logistical framework for physicians and other health care providers to refer to when considering the initiation of medical marijuana therapy. RESULTS: The invited speakers each covered a unique aspect of MMJ therapy for the treatment of chronic pain. These presentations highlighted the current data for and against the use of MMJ as a pain therapy. Optimal patient selection and screening, in addition to policy developments, were discussed. CONCLUSIONS: Increasing interest in MMJ for chronic pain underscores a need for primary care and pain physicians to better understand the indications and evidence for its use free from cultural bias. Given a lack of full conclusive clinical utility, continued research is needed to better understand how to best utilize MMJ therapy for the treatment of chronic pain. Policy initiatives, such as enumerated indications, should follow medical science in order to prevent another abused substance epidemic.

Novel homozygous OPA3 mutation in an Afghani family with 3-methylglutaconic aciduria type III and optic atrophy.

Purpose: To describe and distinguish clinical phenotypes with the overlapping feature of optic atrophy caused by distinct mutations in the same gene, OPA3. We report 3 affected siblings in a consanguineous family harboring a novel OPA3 mutation causing 3-methylglutaconic aciduria type III with optic atrophy.Methods: Retrospective case series.Results: Three siblings (2 male, 1 female) among 6 children in a consanguineous Afghani family developed decreased vision from early childhood. Both parents and all extended family members were unaffected. All 3 affected siblings suffered from severe visual impairment ranging from visual acuities of 20/150 to counting fingers. All had spastic lower extremity weakness and ataxia. Two of the three affected siblings also had a history of seizures, and the female sibling had limited cognition with diffuse atrophic changes on brain MRI. Two of the three individuals also had migraine-like headaches. Urine organic acid analysis revealed mildly elevated 3-methylglutaconic acid for the male siblings. Whole exome sequencing and subsequent PCR confirmation revealed a novel variant in OPA3 (intron1, c.142 + 2_142 + 3dupTG), affecting the consensus sequence of the splice site, for which all 3 clinically affected siblings were homozygous.Discussion: Mutations in OPA3 can cause optic atrophy in a dominant pattern of inheritance associated with cataract or in a recessive pattern associated with spastic paresis and ataxia. The novel recessive mutation and clinical presentations described herein further support how different mutation types affecting OPA3 can produce distinct clinical phenotypes and underscore the critical and susceptible role of mitochondrial health in optic nerve function.

Update on the diagnostic considerations for neurogenic nasal and sinus symptoms: A current review suggests adding a possible diagnosis of migraine.

BACKGROUND: Treatment of rhinosinusitis (RS) is one of the leading reasons for prescriptions of antibiotics, although they often fail to provide symptomatic relief. Appropriately diagnosing and treating patients presenting with RS for whom antibiotic therapy has failed or who have normal CT findings is a controversial topic. One explanation is that what these patients are experiencing is misinformation from the trigeminal nerve and autonomic nervous system. Midfacial pain and pressure with rhinorrhea and nasal congestion do not represent an infectious, or even inflammatory, condition within the sinus or nasal cavities, but a mirage that is best treated as a migraine variant. Observations Although there is not enough research to definitively prove this alternate etiology, we are reaching a tipping point where the clinical implications, real-world experience, and evolving literature support this possible alternate etiology. Four key factors support a midfacial migraine that mimics RS: 1) Pathophysiology: current pathophysiology literature offers a model of how migraine attacks could replicate clinical presentations of RS; 2) Clinical presentation: patients with infectious RS and midfacial migraine have similar symptomatic presentation, similar demographics, but poorly correlated radiological information; 3) Diagnosis: clinical studies support the proposition that there are alternative diagnostic tools for distinguishing patients with midfacial migraine; and 4) Prognosis: Select RS patients show significant improvement with migraine treatment. CONCLUSIONS: We encourage medical professionals to consider migraine disease as a form of sensory misinformation and as a possible etiology of RS complaints. Clinicians can ask validated questions to determine if possible migraine could be an underlying cause, and there are standard preventative treatments for migraine that could alleviate patient symptoms. Dysfunctional vasomotor activity may be the root of the disturbances, particularly when antibiotic therapy fails and CT findings are discordant with symptoms. Until there is a diagnostic test for migraine, clinicians need to question a patient's self-diagnosis of rhinosinusitis. More research is needed to definitively answer this important question.

Cluster Headache and Other Trigeminal Autonomic Cephalalgias.

The trigeminal autonomic cephalalgias are a group of distinct primary headache disorders that share common characteristics of strict unilateral headache often accompanied by unilateral cranial autonomic features. Cluster headache is the most well-known example, but other than neurologists, practitioners often have limited familiarity with these disorders and treatment options. Delays in diagnosis are typical and treatment options remain suboptimal, associated with limited scientific research into these brain disorders. Improved familiarity with core clinical features by health care providers should lead to earlier referral to specialists, and this education is the responsibility of headache medicine specialists. Optimistically, the last few years have seen lobbying for more federal research support in headache medicine and there has been renewed interest by private industry in potential new treatments for trigeminal autonomic cephalalgias.

Migraine Trigger Site Surgery is All Placebo.

BACKGROUND: Over the last decade surgical treatments for migraine involving proposed trigger sites have been described and popularized by plastic surgeons in particular. Various related techniques aim to free up "trigger sites" by removal of small facial muscles or "decompressing" small facial nerves. DISCUSSION: The basis for migraine trigger site surgery is without merit. There is one positive placebo controlled study with many limitations. Natural history and placebo mechanisms explain the outcomes from migraine surgery. The American Headache Society recommends that the migraine surgery not be performed outside of a clinical trial. CONCLUSION: Migraine trigger site surgery should not be performed.

When indomethacin fails: additional treatment options for "indomethacin responsive headaches".

Indomethacin has been used for the treatment of headache disorders since the 1960's, shortly after it was introduced as a treatment for pain and joint swelling in rheumatologic conditions. A subgroup of primary headache disorders, often refractory to other pharmacologic treatment such as triptans and the usual non-steroidal anti-inflammatories, was noted to be exquisitely and absolutely responsive to the analgesic effects of indomethacin. These disorders have been better characterized over the past decade and classified into primary headache disorders of paroxysmal hemicrania (PH) and hemicrania continua (HC). Since the current ICHD-3 beta requires response to indomethacin as a diagnostic criterion, studies on alternative treatments in HC and PH generally occur in patients with intolerance to its gastro-intestinal side effects rather than loss of analgesia effectiveness. More rarely, the development of new headaches have been reported in chronic indomethacin use. In these settings, other classes of medications such as selective cyclooxygenase-2 inhibitors (celecoxib), anti-epileptic agents (topiramate), calcium channel blockers (verapamil, flunarizine), melatonin, and local nerve blocks with anesthetic and steroids have been shown to be effective in case reports and series. We review the literature and provide our clinical recommendations on alternative therapies for the "indomethacin-responsive headaches".

Acupuncture is all placebo and here is why.

BACKGROUND: Alternative and complementary medicines such as acupuncture remain popular with the general public and many clinicians. The term "integrative medicine" is often now used to describe this type of non-science-based medicine, which has become more of a faith-based method of practice, making it harder to challenge. Acupuncture is commonly used to treat headache along with just about any other symptom and condition known to man. DISCUSSION: Physicians regularly fall into many misunderstandings when erroneously believing a real effect from acupuncture, when there is none. A perfunctory and poorly informed media contribute to the misinformation. Sixteen logical traps are identified which together explain most of the false reasoning behind the alleged effect of acupuncture. CONCLUSION: Practitioners need to do a better job of discerning truth from information and data available on acupuncture.

Pseudotumor cerebri pathophysiology.

Pseudotumor cerebri syndrome (PTCS) is an uncommon disorder of raised intracranial pressure of unknown etiology. The signs and symptoms have been well described but the pathogenesis remains a mystery. Most of the evidence suggests increased resistance to cerebrospinal fluid outflow as being pivotal to the disorder. Any comprehensive theory on causation will have to explain the preponderance of obese women of childbearing age with primary PTCS and lack of ventriculomegaly in the disorder. It is possible that female sex hormones, along with endocrinologically active adipose tissue, directly result in the syndrome, in those genetically predisposed. Aldosterone has been proposed also as important in the development of PTCS. Vitamin A, in the form of retinoic acid, may also play a pivotal role, and is influenced by both estrogen and adipose tissue. This article reviews proposed mechanisms of PTCS.

Cannabinoids and hallucinogens for headache.

Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or "marijuana" once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success. The legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy.

Current concepts in refractory migraine.

OPINION STATEMENT: The Refractory or Intractable Migraine (RM) patient has long been a challenge to all healthcare providers (HCP). Headache specialists have recognized this sub group of patients who remain refractory to treatment. Despite this recognition, there are no formal criteria that characterize RM. This article will attempt to provide treatment approaches, some scientifically based and others that are empiric. A reasonable goal is to lessen disability. Combining the various modalities will improve the chances for successful treatment. The foundation of treatment is an emphasis on wellness. This includes optimizing mood, minimizing stress, practicing good sleep hygiene, and avoiding triggers. All comorbid factors should be addressed, including sleep and mood disorders, chronic neck pain, and obesity. Preventive treatment is necessary in the majority of patients, and a plan for "rescue" approaches is essential. Avoiding medication overuse, particularly narcotics, is advisable. Additional options for treatment include onabotulinumtoxinA, and more invasive modalities, such as neurostimulation. Adjunct treatment including supplements and relaxation may also be considered. Keeping a headache calendar is almost mandatory in management with attention to particular headache triggers, patterns and medication overuse (MOH). A trusting physician-patient relationship is also very important and will enhance compliance and foster communication. Patients often lapse from the management plan and the treating physician should be open minded about continuing care. RM is a long-term disease and requires close physician-patient interaction and cooperation for management of the problem. In those RM patients with multiple comorbidities, a multidisciplinary team should optimize management.

Hallucinogens and cannabinoids for headache.

Most hallucinogens and cannabinoids fall into Federal Controlled Substances schedule 1, meaning they cannot be prescribed by practitioners, allegedly have no accepted medical use, and have a high abuse potential. The legal and regulatory status has inhibited clinical research on these substances such that there are no blinded studies from which to assess true efficacy. Despite such classification, hallucinogens and cannabinoids are used by patients with headache on occasion. Cannabinoids in particular have a long history of use for headache and migraine before prohibition and are still used by patients as a migraine abortive. Hallucinogens are being increasing used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and to maintain quiescence for which there is considerable anecdotal success.

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination.

BACKGROUND: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). CONCLUSION: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.

Pharmacological management of neuropathic pain in older adults: an update on peripherally and centrally acting agents.

The burden of neuropathic pain in older adults is great and the practitioner is challenged to reduce symptoms and improve quality of life. Many common neuropathic pain syndromes are more prevalent in the older population, and older adults also carry greater sensitivity to certain side effects. The health care professional should have a thorough familiarity with all medications available to treat this difficult group of disorders.

Adjuvant agents in cancer pain.

Cancer-related neuropathic pain derives from peripheral or central lesions of the nervous system and is often associated with the hallmark symptoms of allodynia (pain from a stimulus that does not normally evoke pain) and hyperalgesia (an exaggerated pain response to a normally painful stimulus). Pain is prevalent in patients with cancer and considerably undermines their quality of life, thereby making the development of a comprehensive pain management approach essential. Coanalgesics have been well integrated into cancer pain management strategies and are often used as first-line options for treatment of certain disease processes such as neuropathic pain. These medicines, including antidepressant and anticonvulsant agents, are recommended by evidence-based guidelines, whereas others, such as lidocaine patch 5%, are supported by randomized, controlled, clinical trial data. In addition to understanding which agents are recommended for neuropathic pain, it is useful to know which agents are of limited utility or are to be avoided when prescribing treatment for neuropathic pain. Notwithstanding the need for head-to-head studies before firm statements on comparative efficacy can be made, it is worth considering the numbers needed to treat statistic for the treatment of neuropathic pain with coanalgesics. Potentially harmful treatments are considered, as well as the numbers needed to treat, mechanisms of action, and clinical trial data for agents that can be beneficial for the management of cancer-associated neuropathic pain.