Pica is known to the medical community as an eating disorder in which individuals may ingest non-food items due to a nutritional deficiency and cause unintentional physical harm to themselves. This article discusses the cases of children with pica in addition to other comorbidities such as trichotillomania, depression, autism, and anxiety. Both patients were trialed on typical first-line treatments to address pica symptoms, including antidepressants, psychotherapy, and neurology consults, which were ineffective in treating pica symptoms. The introduction of naltrexone resulted in significant improvements, including decreased pica symptoms and improvements in depression, anxiety, and overall behaviors. These effects of naltrexone were further bolstered by the effects that occurred when both patients discontinued naltrexone for some time.

This report presents two cases of patients with long-standing, treatment-resistant Hailey-Hailey disease (HHD) who experienced significant symptom relief through a combination therapy of oral naltrexone and dupilumab injections. The therapeutic potential of targeting the Th2 pathway and Ca2+ signaling with dupilumab in managing HHD manifestations is highlighted. The findings suggest that Th2 blockade with dupilumab, in conjunction with naltrexone, effectively controls recalcitrant HHD, indicating a role of cytokine response in altering disease pathogenesis. This case contributes to the growing body of literature on biologic treatments for HHD and suggests avenues for further research in HHD management.

Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.

Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN\'s positive impact on inhibiting the OGF-OGFr axis in cancers. LDN\'s unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions.

UNASSIGNED: Despite the availability of a wide variety of analgesics, many patients with chronic pain often experience suboptimal pain relief in part related to the absence of any medication to address the nociplastic component of common pain syndromes. Low-dose naltrexone has been used for the treatment of chronic pain, typically at 4.5 mg per day, even though it is also noted that effective doses of naltrexone for chronic pain presentations range from 0.1 to 4.5 mg per day. We performed an observational analysis to determine the range of effective naltrexone daily dosing in 41 patients with chronic musculoskeletal pain.
UNASSIGNED: Charts of 385 patients, 115 males, 270 females, ages 18-92, were reviewed. Two hundred and sixty patients with chronic diffuse, symmetrical pain were prescribed a titrating dose of naltrexone to determine a maximally effective dose established by self-report of 1) reduction of diffuse/generalized and/or severity level of pain and/or 2) positive effects on mood, energy, and mental clarity. Brief Pain Inventory and PROMIS scales were given pre- and post-determining a maximally effective naltrexone dose.
UNASSIGNED: Forty-one patients met all criteria for inclusion, successfully attained a maximally effective dose, and completed a pre- and post-outcome questionnaire. Hormesis was demonstrated during the determination of the maximally effective dosing, which varied over a wide range, with statistically significant improvement in BPI.
UNASSIGNED: The maximally effective dose of low-dose naltrexone for the treatment of chronic pain is idiosyncratic, suggesting the need for 1) dosage titration to establish a maximally effective dose and 2) the possibility of re-introduction of low-dose naltrexone to patients who had failed initial trials on a fixed dose of naltrexone.
Low-dose naltrexone (LDN) has been used to treat chronic pain. There is, however, no agreed on effective dose, leaving clinicians without guidelines on initiating treatment with naltrexone. It appears that the dose of LDN for any patient is idiosyncratic, and in a small study, ranges from 0.1 to 6.0 mg/day. Understanding the various possible mechanisms of action of LDN may help the clinician to understand how and why it can effectively reduce chronic pain. A titration schedule to establish the maximally effective dose for chronic myofascial pain is presented.

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Naltrexone is a mu-opioid receptor antagonist increasingly used as an analgesic for chronic pain at low doses. This retrospective, observational cohort study was conducted at an academic medical center to evaluate low-dose naltrexone (LDN) efficacy and describe its use in routine clinical practice. Adults receiving LDN, doses <10 mg for ≥1 month, seen at an outpatient pain clinic from January 1, 2014 to April 1, 2022 were included. The primary outcome was change in the Pain, Enjoyment of Life, and General Activity (PEG) score after LDN. Thirty-one patients were included. Median age was 50 years and 71% were female. Median duration of pain at baseline was 5 years. Mean PEG scores were 7.27 ± 1.39 and 6.62 ± 2.04 at baseline and follow-up, respectively. Mean difference was 0.66 (95% CI [0.10-1.21], p = 0.022). Eighty-seven percent (27) of patients discontinued LDN, 52% (16) for lack of benefit, 23% (7) for loss of benefit, 10% (3) for side effects, and 3% (1) for other reasons. Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.

UNASSIGNED: Fibromyalgia (FM) is a chronic fluctuating, nociplastic pain condition. Naltrexone is a µ-opioid-receptor antagonist; preliminary studies have indicated a pain-relieving effect of low-dose naltrexone (LDN) in patients with FM. The impetus for studying LDN is the assumption of analgesic efficacy and thus reduction of adverse effects seen from conventional pharmacotherapy.
UNASSIGNED: First, to examine if LDN is associated with analgesic efficacy compared with control in the treatment of patients with FM. Second, to ascertain the analgesic efficacy of LDN in an experimental pain model in patients with FM evaluating the competence of the descending inhibitory pathways compared with controls. Third, to examine the pharmacokinetics of LDN.
UNASSIGNED: The study used a randomized, double-blind, placebo-controlled, crossover design and had a 3-phase setup. The first phase included baseline assessment and a treatment period (days -3 to 21), the second phase a washout period (days 22-32), and the third phase a baseline assessment followed by a treatment period (days 33-56). Treatment was with either LDN 4.5 mg or an inactive placebo given orally once daily. The primary outcomes were Fibromyalgia Impact Questionnaire revised (FIQR) scores and summed pain intensity ratings (SPIR).
UNASSIGNED: Fifty-eight patients with FM were randomized. The median difference (IQR) for FIQR scores between LDN and placebo treatment was -1.65 (18.55; effect size = 0.15; P = 0.3). The median difference for SPIR scores was -0.33 (6.33; effect size = 0.13; P = 0.4).
UNASSIGNED: Outcome data did not indicate any clinically relevant analgesic efficacy of the LDN treatment in patients with FM.

Introduction In recent years, low-dose naltrexone has emerged as a novel off-label therapy for many chronic conditions including postural orthostatic tachycardia syndrome (POTS), however, there is little evidence for its efficacy. Methods In this institutional review board (IRB)-approved case series, the charts of six tilt table-confirmed patients with POTS who underwent a trial of low-dose naltrexone (LDN) at our institution were reviewed. Medical history, subjective description of symptom severity, the continuation of therapy, tolerability, and scores on patient-reported outcome measures (Patient-Reported Outcomes Measurement Information System {PROMIS} Fatigue, PROMIS physical and mental health, Generalized Anxiety Disorder Assessment {GAD}-7, Patient Health Questionnaire {PHQ}-9, and Composite Autonomic Symptom Score {COMPASS}) were collected at therapy initiation and six to 12 months after the start of LDN. Results Three out of six reviewed patients reported an improvement in their POTS after the initiation of LDN. Two patients discontinued the therapy due to a lack of perceived benefit. No side effects or adverse outcomes were reported. The patient-reported outcome measures of PROMIS Fatigue, PROMIS physical and mental health, GAD-7, PHQ-9, and COMPASS showed inconsistent changes over the course of therapy, with some patients showing improvement or stability and others showing worsening. The small sample size and incomplete response rate did not allow for extensive statistical analysis. Conclusion As seen in its use in other conditions, LDN appears to have a favorable safety and side effect profile in patients with POTS but has little evidence for efficacy. Although some patients noted benefit, patient-reported outcome measures show a variable response profile. High-quality randomized controlled trials are needed to determine if the treatment is efficacious and should be used outside of a trial basis.

UNASSIGNED: Low-dose naltrexone (LDN) has increased in popularity as a non-opioid medication that may decrease chronic pain symptoms. LDN is most commonly used to treat fibromyalgia, complex regional pain syndrome (CRPS), and painful diabetic neuropathy. Other studies suggest that LDN provides general symptom reduction in inflammatory conditions such as Crohn\'s disease and multiple sclerosis. We reviewed our experience with patients to whom we have prescribed LDN to see what types of painful conditions were most responsive to LDN in our patient population.
UNASSIGNED: Charts from patients who came to the Pain Center between 2014 and 2021 were reviewed.
UNASSIGNED: Of the n = 137 patients who were prescribed LDN, 44% had no evidence of ever filling the prescription, and 4.4% of the responses were not charted. Of the remaining who took LDN (n = 70), 64% had some relief and were designated as \'Responders\'. The most common pain diagnosis was neuropathic pain which, when added to the diagnosis of complex regional pain syndrome, accounted for 51% of responders to LDN. Patients who experienced greater than 50% pain relief from LDN were more likely to have the diagnosis of neuropathic pain or complex regional pain syndrome (p = 0.038, Fisher\'s Exact Test). There was a significant difference in the diagnosis of patients who responded to LDN. Patients with spondylosis were much less likely to respond to LDN when compared with other diagnoses (p = 0.00435, Chi-Square Test).
UNASSIGNED: Patients with all types of neuropathic pain, including CRPS, were significantly more likely to have pain relief from LDN than patients with spondylosis (p=0.018). The diagnosis of spondylosis was more often associated with a lack of response to LDN than any other diagnosis. Patients may need to have a trial of several weeks before analgesic effects are seen with LDN.