Medical Cannabis: A Review from the American Society of Pain and Neuroscience.

Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions. Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported. However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

The Use of Scrambler Therapy in Treating Chronic Pain Syndromes: A Systematic Review.

BACKGROUND: Scrambler therapy (ST) is a noninvasive method of transcutaneous neuromodulation that has 510(K) clearance from the United States Food and Drug Administration for treating acute pain, postoperative pain, and intractable chronic pain. Since its inception, ST has been used to treat many chronic pain syndromes in a variety of patient populations. We synthesized the available literature for ST to delineate its overall evidence basis. MATERIALS AND METHODS: We performed a systematic review based on conventional Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods by surveying multiple data sources from January 1950 through October 2021. Two review authors, independently and in a standardized, unblinded fashion, conducted a systematic review to identify relevant studies and extract the necessary outcome measures. A conservative search strategy was implemented to identify all ST studies for the treatment of chronic pain syndromes. Primary outcome parameters collected were analgesic benefit, adverse effects, and other metrics such as sensorimotor testing. RESULTS: A total of 21 studies met the final criteria for study inclusion and comprised randomized controlled trials (n = 8), prospective observational studies (n = 10), and retrospective cohort studies (n = 3). Nearly all the reported studies explored the use of ST for the treatment of neuropathic pain, with chemotherapy-induced peripheral neuropathy being the most studied condition. Most studies were limited by small cohorts but reported ST being safe, well tolerated, and providing clinically meaningful pain reduction. The duration of posttreatment follow-up ranged from ten to 14 days (concordant with completion of typical ST protocols) to three months. Secondary benefits such as medication reduction and improvement of sensory and motor symptoms were noted by some studies. CONCLUSIONS: ST is regarded as a safe intervention with potential for significant analgesic benefit for neuropathic pain conditions. Although the available evidence is most robust for treating chemotherapy-induced peripheral neuropathy, ST has also been shown to be effective in treating other neuropathic pain syndromes. Evidence for ST use in nociceptive pain conditions is limited but appears promising. The favorable safety profile and increasing evidence basis for ST warrant more extensive recognition and consideration for use in clinical care.

Radiofrequency Ablation for Thoracic and Abdominal Chronic Pain Syndromes.

Chronic thoracic pain and chronic abdominal pain are common conditions that can significantly affect quality of life. Pain syndromes encompassing a variety of causes, including cancer pain, neuritis, and postsurgical pain, are traditionally managed by the use of pharmacologic therapy; however, many cases are refractory to these conservative methods. Radiofrequency ablation (RFA) has been increasingly used as a tool to treat resistant, chronic pain of both thoracic and abdominal origin. Multiple cases and trials have been reported that show the efficacy of RFA in the treatment of these chronic pain conditions.

Chronic Pain in Patients with Rheumatoid Arthritis.

PURPOSE OF REVIEW: Chronic pain is highly prevalent in patients with rheumatoid arthritis (RA) and can cause various physical and psychological impairments. Unfortunately, the appropriate diagnosis of chronic pain syndromes in this population can be challenging because pain may be primary to RA-specific inflammation and/or secondary to other conditions, typically osteoarthritis (OA) and fibromyalgia (FM). This disparity further poses a clinical challenge, given that chronic pain can often be discordant or undetected with standard RA-specific surveillance strategies, including serological markers and imaging studies. In this review, we provide a robust exploration of chronic pain in the RA population with emphasis on epidemiology, mechanisms, and management strategies. RECENT FINDINGS: Chronic pain associated with RA typically occurs in patients with anxiety, female sex, and elevated inflammatory status. Up to 50% of these patients are thought to have chronic pain despite appropriate inflammatory suppression, typically due to peripheral and central sensitization as well as secondary OA and FM. In addition to the standard-of-care management for OA and FM, patients with RA and chronic pain benefit from behavioral and psychological treatment options. Moreover, early and multimodal therapies, including non-pharmacological, pharmacological, interventional, and surgical strategies, exist, albeit with varying efficacy, to help suppress inflammation, provide necessary analgesia, and optimize functional outcomes. Overall, chronic pain in RA is a difficult entity for both patients and providers. Early diagnosis, improved understanding of its mechanisms, and initiation of early, targeted approaches to pain control may help to improve outcomes in this population.

Interventional Therapies for Pain in Cancer Patients: a Narrative Review.

PURPOSE OF REVIEW: Pain is a prevalent symptom in the lives of patients with cancer. In light of the ongoing opioid epidemic and increasing awareness of the potential for opioid abuse and addiction, clinicians are progressively turning to interventional therapies. This article reviews the interventional techniques available to mitigate the debilitating effects that untreated or poorly treated pain have in this population. RECENT FINDINGS: A range of interventional therapies and technical approaches are available for the treatment of cancer-related pain. Many of the techniques described may offer effective analgesia with less systemic toxicity and dependency than first- and second-line oral and parenteral agents. Neuromodulatory techniques including dorsal root ganglion stimulation and peripheral nerve stimulation are increasingly finding roles in the management of oncologic pain. The goal of this pragmatic narrative review is to discuss interventional approaches to cancer-related pain and the potential of such therapies to improve the quality of life of cancer patients.

Incidence, Diagnosis, and Management of Neuromas Following Radiofrequency Ablation Treatment: a Narrative Review.

OBJECTIVE: To determine the epidemiology of neuroma formation as a complication following radiofrequency ablation for chronic pain conditions as well as reviewing the diagnosis and management of neuromas. DESIGN: Evidence-based narrative review and critical appraisal of literature. RESULTS: A comprehensive review of the literature generated one case report describing neuroma formation following lumbar facet medial branch radiofrequency denervation. The rare incidence may be explained by neuroma pathophysiology and peripheral nerve injury produced by radiofrequency ablation, in combination with its asymptomatic nature. Diagnosis of neuromas is predominantly confirmed by clinical history and physical exam with potential for nerve blocks or imaging. Ultrasound has been suggested as a primary imaging modality with magnetic resonance imaging as a secondary option. Neuroma management ranges from conservative therapy to surgery with varying success rates. CONCLUSIONS: Neuroma formation following radiofrequency ablation procedures is exceedingly rare and could be a hypothetical concern in clinical practice. However, the true incidence may be inaccurate given the asymptomatic nature of neuromas.

Management of Lower Extremity Pain from Chronic Venous Insufficiency: A Comprehensive Review.

PURPOSE OF REVIEW: Chronic venous insufficiency is found to some extent in a large proportion of the world's population, especially in the elderly and obese. Despite its prevalence, little research has been pursued into this pathology when compared to similarly common conditions. Pain is often the presenting symptom of chronic venous insufficiency and has significant deleterious effects on quality of life. This manuscript will describe the development of pain in chronic venous insufficiency, and will also review both traditional methods of pain management and novel advances in both medical and surgical therapy for this disease. RECENT FINDINGS: Pain in chronic venous insufficiency is a common complication which remains poorly correlated in recent studies with the clinically observable extent of disease. Although lifestyle modification remains the foundation of treatment for pain associated with chronic venous sufficiency, compression devices and various pharmacologic agents have emerged as safe and effective treatments for pain in these patients. In patients for whom these measures are insufficient, recently developed minimally invasive vascular surgical techniques have been shown to reduce postsurgical complications and recovery time, although additional research is necessary to characterize long-term outcomes of these procedures. This review discusses the latest findings concerning the pathophysiology of pain in chronic venous insufficiency, conservative and medical management, and surgical strategies for pain relief, including minimally invasive treatment strategies.

Radiotherapy-Specific Chronic Pain Syndromes in the Cancer Population: An Evidence-Based Narrative Review.

While radiation therapy is increasingly utilized in the treatment paradigm of many solid cancers, the chronic effects of radiation therapies are poorly characterized. Notably, understanding radiation-specific chronic pain syndromes is paramount given that the diagnosis and management of these conditions can serve to prevent long-standing functional impairments, optimize quality of life, and even allow for continued radiotherapy candidacy. These radiation-specific chronic pain phenomena include dermatitis, mucositis, enteritis, connective tissue fibrosis, lymphedema, and neuropathic pain syndromes. It is necessary to maintain a low threshold of suspicion for appropriately diagnosing these conditions as there exists a variance in when these symptoms arise after radiation. However, we present key epidemiological data delineating vulnerable cancer populations for each pain syndrome along with the available evidence for the management for each specific condition.

Interventional Radiofrequency Treatment for the Sympathetic Nervous System: A Review Article.

INTRODUCTION: Interventional techniques such as radiofrequency (RF) treatment can be used to interrupt pain signals transmitted through the sympathetic nervous system (SNS). RF treatments including the pulsed (PRF) and continuous (CRF) modalities show enhanced control over lesion size and enhanced ability to confirm accurate positioning compared to other interventional methods. PRF also acts to reduce the area of the lesion. In this article, we characterize the currently available evidence supporting the use and efficacy of RF treatments in sympathetically mediated pain (SMP) conditions. STUDY DESIGN: A comprehensive literature review. METHODS: A PubMed and Cochrane Library database search was performed for human studies applying RF treatment at sympathetic sites (sphenopalatine ganglion, stellate ganglion, cervical, thoracic, or lumbar sympathetic ganglia, celiac plexus, splanchnic nerves, superior hypogastric plexus, and ganglion impar) between January 1970 to May 2020. Data were extracted, summarized into tables, and qualitatively analyzed. RESULTS: PRF and CRF both show promise in relieving SMP conditions, such as complex regional pain syndrome (CRPS), pain in the perineal region, headache and facial pain, and oncologic and non-oncologic abdominal pain, in addition to other types of pain, with minimal complications. Furthermore, in most comparative studies, outcomes using RF treatments exceeded other interventional techniques, such as anesthetic block and chemical neurolysis. CONCLUSIONS: RF treatments can be effective in carefully selected patients who are refractory to conservative management. However, further randomized controlled studies are needed prior to implementing it into common practice.

Observations of Autonomic Variability Following Central Neuromodulation for Chronic Neuropathic Pain in Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) persons with chronic neuropathic pain (NP) demonstrate maladaptive autonomic profiles compared to SCI counterparts without NP (SCI - NP) or able-bodied (AB) controls. These aberrations may be secondary to maladaptive neuroplasticity in the shared circuitry of the pain neuromatrix-central autonomic network interface (PNM-CAN). In this study, we explored the proposed PNM-CAN mechanism in SCI + NP and AB cohorts following centrally-directed neuromodulation to assess if the PNM and CAN are capable of being differentially modulated. MATERIALS AND METHODS: Central neuromodulation was administered via breathing-controlled electrical stimulation (BreEStim), previously evidenced to operate at the PNM. To quantify CAN activity, conventional heart rate variability (HRV) recordings were used to gather time and frequency domain parameters of autonomic modulation. SCI + NP (n = 10) and AB (n = 13) cohorts received null and active BreEStim randomly in crossover fashion. HRV data were gathered pretest and 30 minutes posttest. Pain modulation was quantified at both time-points by visual analog scale (VAS) for SCI + NP persons and electrical detection and pain threshold levels (EDT, EPT) for AB persons. RESULTS: Following active BreEStim only, SCI + NP persons demonstrated increased parasympathetic tone (increased NN50, p = 0.03, and pNN50, p = 0.02, HRV parameters). This parasympathetic restoration was associated with analgesia (VAS reduction, p < 0.01). Similarly, AB persons demonstrated increased noxious tolerance (increased EPT, p = 0.03, with preserved EDL, p = 0.78) only following active BreEStim. However, this increased pain threshold was not associated with autonomic changes. CONCLUSIONS: Central modulation targeting the PNM produced autonomic changes in SCI + NP persons but not AB persons. These findings suggest that AB persons exhibit intact CAN mechanisms capable of compensating for PNM aberrations or simply that SCI + NP persons exhibit altered PNM-CAN machinery altogether. Our collective findings confirm the interconnectedness and maladaptive plasticity of PNM-CAN machinery in SCI + NP persons and suggest that the PNM and CAN circuitry can be differentially modulated.

Cannabis Use in Hospitalized Patients with Chronic Pain.

INTRODUCTION: To date, no study has reported the prevalence of cannabis use in chronic pain patients. The aim of this study is to investigate the trends in cannabis use among chronic pain in-patients from 2011 to 2015 in the USA. METHODS: Patients were identified from the National Inpatient Sample (NIS) database using the International Classification of Diseases, Ninth and Tenth Revision, diagnosis codes for chronic pain and cannabis use. Annual estimates and trends were determined for cannabis use, patient characteristics, cannabis use among subgroups of chronic pain conditions, cost, length of stay, and associated discharge diagnosis. RESULTS: Between 2011 to 2015, a total of 247,949 chronic pain patients were cannabis users, increasing from 33,189 to 72,115 (P < 0.001). There were upward trends of cannabis use in females (38.7-40.7%; P = 0.03), Medicare insured patients (32.7-40.4%; P < 0.01), patients with lowest annual household income (36.1-40.9%; P = 0.02), patients aged 45-64 years (45.9-49.2%; P < 0.001), and patients with tobacco use disorder (63.8-72.4%; P < 0.0001). Concurrently, cannabis use decreased among patients with opioid use disorder (23.8-19.9%; P < 0.001). Cannabis use increased from 2011 to 2015 in patients with chronic regional pain syndrome, trauma, spondylosis, and failed back surgery syndrome. Adjusted total hospitalization cost increased from $31,271 ($1333) in 2011 to $38,684 ($946) in 2015 (P < 0.001). CONCLUSIONS: Cannabis use increased substantially from 2011 to 2015, while the rates of cannabis use in opioid users down-trended simultaneously. Disparities in cannabis use among subgroups should be explored further.

Acute Inflammation in Traumatic Brain Injury and Polytrauma Patients Using Network Analysis.

INTRODUCTION: Traumatic brain injury (TBI) is associated with secondary injury to the central nervous system (CNS) via inflammatory mechanisms. The combination of polytrauma and TBI further exacerbates the inflammatory response to injury; however, combined injury phenomena have not been thoroughly studied. In this study, we examined the inflammatory differences between patients with TBI versus patients with polytrauma, but no TBI (polytrauma). We hypothesize that patients with TBI have a heightened early inflammatory response compared with polytrauma. METHODS: We conducted a single-center retrospective study of a cohort of patients with polytrauma, who were enrolled in the PROPPR study. These patients had blood samples prospectively collected at eight time points in the first 3 days of admission. Using radiological data to determine TBI, our polytrauma cohort was dichotomized into TBI (n = 30) or polytrauma (n = 54). Inflammatory biomarkers were measured using ELISA. Data across time were compared for TBI versus polytrauma groups using Wilcoxon rank-sum test. Network analysis techniques were used to systematically characterize the inflammatory responses at admission. RESULTS: Patients with TBI (51.6%) had a higher 30-day mortality compared with polytrauma (16.9%) (P <0.001). Expression levels of IL6, IL8, and CCL2 were elevated from the 2-h through 24-h time points, becoming significant at the 6-h time point (IL6, IL8, and CCL2; P <0.05) (). CSF3 showed a similar pattern, but did not attain significance. TBI and polytrauma networks underwent diverging trends from admission to the 6-h time point. CONCLUSION: Patients with TBI demonstrated upregulations in proinflammatory cytokines IL6, IL8, and CCL2. Utilizing informatics methods, we were able to identify temporal differences in network trends, as well as uncharacterized cytokines and chemokines in TBI. These data suggest TBI induces a distinct inflammatory response and pathologically heightened inflammatory response in the presence of polytrauma and may propagate worsened patient outcomes including mortality.

Neuropathic pain modulation after spinal cord injury by breathing-controlled electrical stimulation (BreEStim) is associated with restoration of autonomic dysfunction.

BACKGROUND: Recent findings have implicated supraspinal origins from the pain neuromatrix- central autonomic network (PNM-CAN) in the generation of neuropathic pain (NP) after spinal cord injury (SCI). The aim of this study was to further investigate the theorized PNM-CAN mechanisms in persons with SCI by using a centrally directed pain intervention, provided by breathing-controlled electrical stimulation (BreEStim), to measure resultant autonomic changes measured by time and frequency domain heart rate variability (HRV) analysis. METHODS: Null and active BreEStim interventions were administered to SCI+NP subjects (n=10) in a random order. HRV data and VAS pain scores were collected at resting pre-test and 30 minutes post-test time points. Resting HRV data were also collected from SCI-NP subjects (n=11). RESULTS: SCI+NP subjects demonstrated a lower baseline HRV and parasympathetic tone, via SD of the normal-to-normal intervals (SDNN) and low frequency (LF) parameters, compared with SCI-NP subjects. However, following active BreEStim, SCI+NP subjects exhibited an increase in HRV and parasympathetic tone, most notably via pairs of successive R-R beat lengths varying by greater than 50 ms (NN50) and proportion of NN50 for total number of beats (pNN50) parameters along with lower VAS scores. Additionally, the post-test SCI+NP group was found to have a statistically comparable autonomic profile to the SCI-NP group across all HRV variables, including SDNN and LF parameters. CONCLUSION: The analgesic effects of active BreEStim in SCI+NP subjects were associated with restoration of autonomic dysfunction in this population.