Effective Doses of Low-Dose Naltrexone for Chronic Pain - An Observational Study.

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Soft Tissue: A Possible Source of Pain Pre and Post Minimally Invasive Spine Surgery.

STUDY DESIGN: Case studies. OBJECTIVES: To demonstrate that muscle generated pain (MGP) may be a cause of pain in patients who have undergone minimally invasive spine surgery (MISS). METHODS: A physical examination including electrical stimulation of putative pain generating muscles to identify the presence of lowered thresholds for depolarization of muscle nociceptors, and an examination of strength and flexibility of key muscles in the upper and lower body, may identify multiple etiologies of MGP. Treatment of identified muscles consisted of muscle/tendon injections to identified sensitized muscles followed by exercises incorporating relaxation limbering and stretching. RESULTS: Postsurgical pain was eliminated and mobility restored in both presented cases replicating success in prior published studies. CONCLUSIONS: Understanding the pathophysiological mechanisms of muscle pain may facilitate the evaluation and treatment of MGP in MISS patients diagnosed with failed back surgery syndrome.

Two-Year Follow-Up and Remodeling Kinetics of ChonDux Hydrogel for Full-Thickness Cartilage Defect Repair in the Knee.

OBJECTIVE: To determine performance and repair kinetics of the ChonDux hydrogel scaffold for treating focal articular cartilage defects in the knee over 24 months. DESIGN: This assessor-blinded trial evaluates ChonDux hydrogel scaffold implantation in combination with microfracture in 18 patients across 6 sites. Male and female patients 18 to 65 years of age with full-thickness femoral condyle defects 2 to 4 cm2 in area were enrolled. Eligible patients received ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI relaxation time and patient surveys via visual analogue scale (VAS) pain and International Knee Documentation Committee (IKDC) knee function scoring. RESULTS: ChonDux maintained durable tissue restoration over 24 months with final defect percent fill of 94.2% ± 16.3% and no significant loss of fill volume at any time points. Tissues treated with ChonDux maintained T2 relaxation times similar to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased between 1 and 6 weeks, and IKDC knee function scores improved by approximately 30.1 with ChonDux over 24 months. CONCLUSION: ChonDux treatment is a safe adjunct to microfracture therapy and promotes stable restoration of full thickness articular cartilage defects for at least 24 months.

A preliminary study to determine if a muscle pain protocol can produce long-term relief in chronic back pain patients.

OBJECTIVE: To assess the effectiveness of a muscle protocol to treat patients diagnosed with neuraxial low back pain (LBP) before and after invasive treatments. DESIGN: Patients with chronic (>6 months) LBP-postinvasive treatment and pre-spine surgery-were assessed and treated. An electrical device rather than palpation was used to determine muscle(s) as possible sources of pain. Patients testing positive for muscle pain were treated with a comprehensive protocol and were followed for >3 months to determine the effect of treatment on pain severity and interference in function. RESULTS: Study 1: In 56 (postinvasive treatment) patients who had failed back surgery, epidural steroid injections, facet blocks, and/or trigger point injections, mean Brief Pain Inventory (BPI) pain severity dropped from 5.54 at baseline to 3.96 (P < 0.001) at a median follow-up of 77 weeks; mean BPI interference dropped from 6.09 to 3.4 (P < 0.001). Fifty-two percent of respondents reported over 50% relief. Study 2: Three of seven patients originally scheduled for spine surgery completed a substantial part of the muscle protocol, canceled their surgeries, and obtained significant relief at the 16-19 month follow-up point. CONCLUSION: In patients thought to have neuraxial pain, identification and treatment of painful muscles had statistically significant long-lasting and clinically meaningful reductions in pain and improvement in function. Muscle and tendon attachments may be an important and treatable source of pain in patients diagnosed with pre and postsurgical neuraxial pain.

Human cartilage repair with a photoreactive adhesive-hydrogel composite.

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.

A comprehensive protocol to diagnose and treat pain of muscular origin may successfully and reliably decrease or eliminate pain in a chronic pain population.

OBJECTIVE: A comprehensive protocol is presented to identify muscular causes of regional pain syndromes utilizing an electrical stimulus in lieu of palpation, and combining elements of Prolotherapy with trigger point injections. METHODS: One hundred seventy-six consecutive patients were evaluated for the presence of muscle pain by utilizing an electrical stimulus produced by the Muscle Pain Detection Device. The diagnosis of "Muscle Pain Amenable to Injection" (MPAI), rather than trigger points, was made if pain was produced for the duration of the stimulation. If MPAI was found, muscle tendon injections (MTI) were offered to patients along with post-MTI physical therapy, providing neuromuscular electrical stimulation followed by a validated exercise program [1]. A control group, evaluated 1 month prior to their actual consultation/evaluation when muscle pain was identified but not yet treated, was used for comparison. RESULTS: Forty-five patients who met criteria completed treatment. Patients' scores on the Brief Pain Inventory decreased an average of 62%; median 70% (P < 0.001) for pain severity and 68%; median 85% (P < 0.001) for pain interference one month following treatment. These changes were significantly greater (P < 0.001) than those observed in the untreated controls. CONCLUSION: A protocol incorporating an easily reproducible electrical stimulus to diagnose a muscle causing pain in a region of the body followed by an injection technique that involves the entirety of the muscle, and post injection restoration of muscle function, can successfully eliminate or significantly reduce regional pain present for years.

Protein profile of osteoarthritic human articular cartilage using tandem mass spectrometry.

Articular cartilage contains both chondrocyte cells and extracellular matrix (ECM) components. Currently, comprehensive information concerning the protein composition of human articular cartilage tissue is somewhat lacking. In this report we detail the use of tandem mass spectrometry (MS/MS) for a preliminary global identification of proteins from human articular knee cartilage tissue from patients diagnosed with osteoarthritis. Knee cartilage supernatant was fractionated using one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE), in-gel digested and peptide sequences were then determined by performing on-line nano-liquid chromatography (LC)/MS/MS experiments using an ion trap mass spectrometer. Altogether, over 100 different proteins from nearly 700 unique peptide sequences were detected by MS/MS. The majority of the proteins identified are involved in ECM organization (35%), signal transduction and cell communication (14%), immune response (11%) and metabolism and energy pathways (11%). Proteins observed included several well-known cartilage components as well as lower abundant lesser known ECM proteins. Possible degradation products in the cartilage sample, such as from cartilage link protein, could also be detected by our mass spectrometry methods. We show here that mass spectrometry can be utilized as a tool for a fast, accurate and sensitive analysis of a complex mixture of cartilage proteins. It is believed that this type of proteomic analysis will aid future work centered on investigating the pathology of this and other related joint diseases.

Pain in cancer patients unrelated to the cancer or treatment.

The majority of patients with cancer will experience pain in the course of their disease [Kjaer, M. The therapy of cancer pain and its integration into a comprehensive supportive care strategy. Ann. Oncol. 1997, 8 (3), 15-19; Bruera, E.; Lawlor, P. Cancer pain management. Acta Anaesthesiol. Scand. 1997, 41 (1 of 2), 146-153]. Epidemiological studies [Foley, K.M. The treatment of pain in the patient with cancer. CA Cancer J. Clin. 1986, 36 (4), 194-215; Walley, B.A.; Hagen, N.A. The epidemiology of cancer pain. Pain Dig. 1995, (5) 237-244; Portenoy, R.K. Cancer pain: epidemiology and syndromes. Cancer 1989, 63 (11), 2298-2307] generally categorize the pain as 1) directly caused by the neoplastic process or related phenomena; 2) by treatment; or 3) unrelated to the neoplastic process. In approximately 10% of cancer patients who have pain, the pain is unrelated to the disease or treatment and is most often caused by muscles and connective tissue (Twycross, R. Pain Relief in Advanced Cancer; Churchill Livingstone: New York, 1994; 55-61). An overview of pathophysiological mechanisms of muscle pain is presented, followed by a structured protocol to treat frequently encountered pain of muscular origin. The purpose of this article is to provide to the practicing clinicians easy to apply approaches for the treatment of muscle-related pain.

Failure to diagnose pain of muscular origin leads to unnecessary surgery.

Three patients who were scheduled for surgical procedures for a variety of diagnoses are presented. Each of the patients presented with pain that was interpreted as a result of an operable lesion. None of the patients was assessed for a possible muscular etiology of their pain prior to being evaluated at the author's pain center. In all three patients, muscles were identified that replicated their pain. Each patient received treatment to his or her pain-producing muscles. None of the contemplated surgeries was performed.