Faculty Bibliography

Introduction: Dental pain is primarily treated by dentists and emergency medicine clinicians and may occur because of insult to the tooth or oral surgery. The dental impaction pain model (DIPM) has been widely used in clinical studies of analgesic agents and is generalizable to many other forms of pain.Areas Covered: The authors discuss the DIPM, which has allowed for important head-to-head studies of analgesic agents, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations. Postsurgical dental pain follows a predictable trajectory over the course of one to 3 days. Dental pain may have odontic origin or may be referred pain from other areas of the body.Expert opinion: Pain following oral surgery has sometimes been treated with longer-than-necessary courses of opioid therapy. Postsurgical dental pain may be moderate to severe but typically resolves in a day or two after the extraction. Opioid monotherapy, rarely used in dentistry but combination therapy (opioid plus acetaminophen or an NSAID), was sometimes used as well as nonopioid analgesic monotherapy. The dental impaction pain model has been valuable in the study of analgesics but does not address all painful conditions, for example, pain with a neuropathic component.

(1) Spinal Cord Microglial Phenotypic Changes Following Sciatic Nerve Crush in CD137LKO Mice / David Nicholas, Kinuyo Ohara, Ling Cao -- (2) Notalgia Paresthetica Successfully Treated with Cervical Epidural Injection and Occipital Nerve Block: A Case Report / Fabienne Saint-Preux, Justin Mendoza, Salvador Portugal

Purpose Painful neuropathy or peripheral neuropathic pain (PNP) is a common neurological condition estimated to affect ~7-8% of the general population in Europe. Managing patients with PNP is challenging; it often becomes chronic and can have a significant impact on quality of life. According to the revised International Association for the Study of Pain (IASP) recommendations for ICD11, PNP is considered to be a distinct chronic pain condition (Scholz et al., 2019)1. Postherpetic neuralgia (PHN) following shingles infection, has specifically been named as one of the PNP conditions. High concentration 8% capsaicin patch (HCCP) is commonly recommended as a second line therapy for PHN. HCCP is indicated for the treatment of peripheral neuropathic pain (PNP) in the EU and for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and for neuropathic pain associated with diabetic peripheral neuropathy (DPN) of the feet in the US. Capsaicin is a highly selective, potent and highaffinity exogenous agonist for the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors which, through a combination of activities, defunctionalizes nociceptor fibers and reduces cutaneous hypersensitivity. As a result, capsaicin is an attractive peripherally acting treatment to control localized pain, hyperalgesia, or allodynia (Anand and Bley, 2011)2. The HCCP delivers the drug effectively and directly to the skin while limiting the risk of systemic effects and drug interactions. Whilst controlled trials have demonstrated the safety and effectiveness of capsaicin patches, the STRIDE study was designed to investigate the long-term safety of repeated patch administration in patients with non-diabetic neuropathic pain (Galvez et al., 2017)3. The present analysis considers the effect on treatment outcomes among a subgroup of patients with PHN included in the STRIDE study. Methods The STRIDE study was an open-label, multicenter, 52-week observational trial conducted in Europe. A diagnosis of PHNwas based on pain persisting since shingles vesicle crusting, for a minimum of 3 months. Prior treatment with capsaicin patches and a history of diabetes were among the exclusion criteria. Patients received up to 6 capsaicin 640 g/cm2 (8% weight for weight) HCCP treatments at 9-to 12-week intervals. At each application visit, a maximum of 4 patches equivalent to an area of up to 1120 cm2 were applied for 60 minutes. HCCP retreatment was at the investigator's discretion and according to patient feedback. Long-term tolerability and safety were the primary objectives of the study. In addition, areas of spontaneous pain and allodynia were monitored, and various scales were used to assess pain, quality of life and overall treatment outcome at each retreatment assessment timepoint. Descriptive statistics (including means and standard deviations) are presented; missing observations were not imputed. Results Of the 107 PHN patients included in the study, 66 completed the trial. The reason for withdrawal was lack of efficacy (14.95%), adverse events in (4.67%) and other reasons (18.69%). HCCP was applied once in 22 patients, twice in 26, three times in 24 and >=4 times in 35. All but 1 patient used preapplication topical anesthesia during the study, and 79.4% used concomitant medications for neuropathic pain. 73% of patients experienced possible or probable drugrelated adverse events, mostly associated with transient application site reactions (57.9%). The maximum severity was mild or moderate in 57% of cases, and only 1 drug-related event required treatment discontinuation. The average daily pain score was reduced from a baseline value of 6.6 (SD, 1.46) to 5.0 (1.99) after 6 months and 4.6 (2.18) after 12 months. The overall change in mean daily pain intensity by the end of study was approximately -1.7. The proportion of responders (>=30% decrease from baseline on a Numerical Pain Rating Scale) progressively increased during the study, to 22.7% after 3 months, and 33.3% and 39.7% after 6 and 12 months, respectively. Over 50% of patients showed at least minimal improvement according to the assessment of their condition by the end of study. The area of allodynia/ hyperplasia and the extent of spontaneous pain (reported in most patients at baseline, mainly on the torso) decreased during the study by just over 20%. Conclusions HCCP repeat application over 12 months in patients with PHN was well tolerated, with mostly transient local adverse events directly linked to the site of application. Progressive and sustained reduction in pain intensity was achieved, as well as reductions in the area of allodynia and spontaneous pain. Overall, the findings from this study demonstrate that repeated HCCP application is a well-tolerated and effective long-term treatment option in patients with PHN

BACKGROUND:Interlaminar and transforaminal epidural steroid injections (ILESI and TFESI) are commonly performed procedures. However, the United States Food and Drug Administration has required the addition of drug warning labels for injectable corticosteroids. Updated evidence and scrutiny from regulatory agencies may affect practice patterns. OBJECTIVE:To characterize TFESI practices as well as to provide an update on periprocedural practices for any type of epidural steroid injection (ESI), we surveyed pain medicine physicians in the United States. STUDY DESIGN AND SETTING/METHODS:This was a cross-sectional survey of pain medicine physicians in the United States. METHODS:A web-based survey was distributed to pain medicine physicians in the United States selected from the Accreditation Council for Graduate Medical Education accredited pain medicine fellowship program list as well as the American Society of Interventional Pain Physicians membership database. Physicians were queried about TFESI practices, including needle size, use of image guidance, methods to detect vascular uptake, and preference for injectate. RESULTS:A total of 249 responses were analyzed. Only a minority of respondents reported performing cervical TFESI. There were variations in needle size, methods to detect vascular uptake, and choice of injectate. There were also variations in monitoring practices. LIMITATIONS/CONCLUSIONS:The response rate is a limitation. Thus the results may not be representative of all US pain medicine physicians. CONCLUSIONS:Though all respondents used image guidance for TFESI, variations in other TFESI practices exist. There are also differences in periprocedural practices. Since the closure of this survey, a multisociety pain workgroup published recommendations regarding ESI practices. Our survey findings support the need for more evidence-based guidelines regarding ESI. KEY WORDS/UNASSIGNED:Epidrual steroid injections, transforaminal epidural steroid injection, steroids, local anesthetic, survey, interventional pain.

Fear of withdrawal symptoms has been cited by survey respondents as the main reason that they continued to use opioids. Lofexidine is an α₂-adrenergic agonist that decreases the sympathetic outflow that results in the characteristic symptoms of opioid withdrawal. A structural analog of clonidine, lofexidine has a higher affinity and specificity for the α_2a receptors and does not reinforce opioid dependence. Withdrawal symptoms correlate approximately to the half-life of the opioid; patient factors such as age, duration of opioid exposure, physical status, and other considerations may influence the nature and duration of withdrawal symptoms. For patients with opioid use disorder and psychiatric comorbidities, withdrawal may be destabilizing and may exacerbate mental health status. Lofexidine has been shown in clinical trials to be safe and effective in helping to manage the symptoms of withdrawal and has been recommended in guidelines for this purpose. Adverse events associated with lofexidine include QT prolongation, hypotension, orthostasis, and bradycardia. The maximum course of treatment is 14 days, and doses should be titrated, with the recommended maximum dose to coincide with the most severe withdrawal symptoms (about 5-7 days after opioid discontinuation).

BACKGROUND:Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options. METHODS:The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer-reviewed literature as the basis for making Minimally Invasive Spine Treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using United States Preventive Services Task Force (USPSTF) criteria. The Consensus Group also created a treatment algorithm. Literature searches found 9 studies (2 randomized controlled trials or RCTs; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers. RESULTS:The LSS treatment choice is dependent on the degree, spinal or anatomic level, and architecture of the stenosis, the severity of the symptoms, failed, past, less-invasive treatments, previous fusions or other open surgical approaches, and patient comorbidities. There is Level I evidence for percutaneous image-guided lumbar decompression (PILD) as superior to lumbar epidural steroid injection, and 1 RCT supporting spacer use in a non-inferiority study comparing 2 spacer products currently available. CONCLUSIONS:Minimally invasive spine treatments should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer-reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence-based decision algorithm.

BACKGROUND:Previous surveys have identified variations in practice patterns related to epidural steroid injections. Since then, the United States Food and Drug Administration (FDA) has required the addition of drug warning labels for injectable corticosteroids. Updated evidence, as well as scrutiny from regulatory agencies, may affect practice patterns. OBJECTIVE:To provide an update on interlaminar epidural steroid injection (ILESI) practice patterns, we surveyed interventional pain management (IPM) physicians in the United States. STUDY DESIGN AND SETTING/METHODS:This was a cross-sectional survey of IPM physicians in the United States. METHODS:A web-based survey was distributed to IPM physicians in the United States selected from the Accreditation Council for Graduate Medical Education accredited pain medicine fellowship program list as well as the American Society of Interventional Pain Physicians membership database. Physicians were queried about ILESI practices, including needle size, use of image guidance, level of injection, identification of the epidural space, and preference for injectate. RESULTS:A total of 249 responses were analyzed. All respondents used image guidance for ILESI. There were variations in needle size, use of contrast, number of fluoroscopic views utilized, technique for identifying the epidural space, and choice of injectate. LIMITATIONS/CONCLUSIONS:The response rate is a limitation, thus the results may not be representative of all United States IPM physicians. CONCLUSIONS:Though all respondents used image guidance for ILESI, variations in other ILESI practices still exist. Since the closure of this survey, a multi-society pain workgroup published recommendations regarding ESI practices. Our survey findings support the need for more evidence-based guidelines regarding ESI. KEY WORDS/UNASSIGNED:Epidural injection, epidural steroids, survey, low back pain, neck pain, technique.

OBJECTIVES: To report the opioid-sparing effects of SoluMatrix indomethacin, developed using SoluMatrix Fine Particle Technology, in a phase 3 study in patients with acute pain following bunionectomy. METHODS: This phase 3, placebo-controlled study randomized 462 patients with moderate-to-severe pain following bunionectomy surgery to receive SoluMatrix indomethacin 40 mg three times daily, SoluMatrix indomethacin 40 mg twice daily, SoluMatrix indomethacin 20 mg three times daily, celecoxib 400-mg loading dose followed by 200 mg twice daily, or placebo. Patients were permitted to receive opioid-containing rescue medication throughout the study. The proportion of patients who used rescue medication and the amount of rescue medication used on the first (0-24 h) and second (>24-48 h) days following initial dose of study medication, as well as time to first rescue medication use, were assessed. RESULTS: Significantly fewer patients who received SoluMatrix indomethacin 40 mg or 20 mg three times daily used opioid-containing rescue medication on day 1 compared with those receiving placebo (P