The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study.

INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.

Neuropathic Corneal Pain as Debilitating Manifestation of LONG-COVID.

This report illustrates the case of a female patient suffering from severe ocular discomfort, tinnitus and ageusia, 7 months after a SARS-CoV-2 infection. The medical history implicated a diagnosis of LONG-COVID with ocular pain as the most debilitating symptom. In-vivo confocal microscopy revealed corneal microneuromas with hyperreflectivity and irregular enlargement of nerve endings in both eyes, which led to the diagnosis of neuropathic corneal pain. The aim of this report is to increase awareness that COVID-19 induced neuropathic pain can also occur in the cornea representing the human body's most richly innervated tissue.

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial.

BACKGROUND: Several studies have shown that cholinergic mechanisms play a pivotal role in the anti-nociceptive system by acting synergistically with morphine and reducing postoperative opioid consumption. In addition, the anti-cholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects. METHODS: In this randomised placebo-controlled trial including 110 patients undergoing nephrectomy, we evaluated the effects of intraoperative physostigmine 0.5 mg h-1 i.v. for 24 h on opioid consumption, hyperalgesia, pain scores, and satisfaction with pain control. RESULTS: Physostigmine infusion did not affect opioid consumption compared with placebo. However, the mechanical pain threshold was significantly higher (2.3 [sd 0.3]) vs 2.2 [0.4]; P=0.0491), and the distance from the suture line of hyperalgesia (5.9 [3.3] vs 8.5 [4.6]; P=0.006), wind-up ratios (2.2 [1.5] vs 3.1 [1.5]; P=0.0389), and minimum and maximum postoperative pain scores at 24 h (minimum 1.8 [1.0] vs 2.4 [1.2]; P=0.0451; and maximum 3.2 [1.4] vs 4.2 [1.4]; P=0.0081) and 48 h (minimum 0.9 [1.0] vs 1.6 [1.1]; P=0.0101; and maximum 2.0 [1.5] vs 3.2 [1.6]; P=0.0029) were lower in the study group. Pain Disability Index was lower and satisfaction with pain control was higher after 3 months in the physostigmine group. CONCLUSIONS: In contrast to previous trials, physostigmine did not reduce opioid consumption. As pain thresholds were higher and hyperalgesia and wind-up lower in the physostigmine group, we conclude that physostigmine has anti-hyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control. CLINICAL TRIAL REGISTRATION: EudraCT number 2012-000130-19.

The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial.

INTRODUCTION: Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model. METHODS: This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control. RESULTS: Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity. CONCLUSIONS: Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects-especially in the absence of reported side effects-make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.

The Effect of the Modified Lateral Suprascapular Block on Shoulder Function in Patients With Chronic Shoulder Pain.

BACKGROUND: Suprascapular nerve block (SSNB) is commonly used in pain therapy for patients with chronic shoulder pain. The effect of SSNB on shoulder function has, however, not been investigated so far. If in shoulder function, i.e. the range of motion is increased after application of the nerve block, it can be expected that subsequent physiotherapy, besides being less painful, is also more effective in terms of restoring shoulder mobility. OBJECTIVES: Our aim was to evaluate the effect of SSNB on shoulder function, in patients with chronic shoulder pain. PATIENTS AND METHODS: Patients were evaluated using the Constant-Murley Score (CMS) and number rating scale values for pain. The SSN was blocked using the Feigl approach, with 5 ml ropivacaine 0.5%. Shoulder function and pain were assessed 60 minutes and 24 hours after the block. RESULTS: Totally, 20 patients completed the study. The CMS and pain scores significantly improved after the block. CONCLUSIONS: The use of the modified lateral SSNB of Feigl significantly reduces pain and increases shoulder function, in chronic shoulder pain.

Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

OBJECTIVES: The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). MATERIALS AND METHODS: In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. RESULTS: All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. CONCLUSIONS: This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal.

Modified lateral block of the suprascapular nerve: a safe approach and how much to inject? A morphological study.

BACKGROUND AND OBJECTIVES: This paper presents an evaluation of a modified lateral suprascapular nerve block with easy orientation, low risk of displacement of the needle, and with an assessment of 2 different volumes to propose an ideal volume for a successful block. METHODS: Both shoulders of 34 cadavers were investigated. Insertion point of the needle was determined in the angle of the lateral end of the clavicle, acromion, and the spine of the scapula. The needle was directed toward the medial, dorsal, and caudad direction. Ten mL of diluted contrast agent for computerized tomography was injected in the 34 right sides (group A) and 5 mL in the 34 left sides (group B). Immediately after injection, all shoulders were investigated by computerized tomography scans and 3-dimensional reconstruction to document the constrast dissemination. Five sides of each group were injected with colored contrast and dissected after computerized tomography investigation. RESULTS: Group A showed a distribution to the entire supraspinous fossa in all cases and the contrast was pressed out of the suprascapular notch in 4 cases with a maximal extension into the axillary fossa in 3 cases. In group B, the supraspinous fossa was filled in 24 cases, with a maximal extension to the axillary fossa in 2 cases. In 9 cases, the contrast agent stayed in the lateral half of the supraspinous fossa. In 1 case we had a medial spread only which still surrounded the suprascapular notch, in another case a superficial spread with misplacement of the needle. CONCLUSION: Based on this cadaver study, the lateral modified approach appears to be a safe technique for a suprascapular nerve block, which might be preferred as a single shot technique. A 5 mL volume appears sufficient to fill the supraspinous fossa and to reach the suprascapular nerve, which branches in this anatomical compartment.

Radiation dose reduction in invasive cardiology by restriction to adequate instead of optimized picture quality.

In this study, the cinegraphic image intensifier entrance dose level for coronary angiography was changed in four steps from dose level A (0.041 microGy frame(-1)), allowing high contrast, but coarse mottled background, to level D (0.164 microGy frame(-1)), affording high transparency and sharpness. Using this new approach throughout the course of 404 consecutive cardiac catheterizations, we reduced patient radiation exposures down to 11 to 16% of currently typical values: i.e., mean dose area products of 5.97 Gy cm2 (n = 91), 6.73 (n = 113), 8.11 (n = 91), and 8.90 (n = 109); cinegraphic dose area products of 2.34, 3.64, 4.56, and 5.49; and cinegraphic dose area products frame(-1) of 13.3, 19.8, 27.0, and 30.2 mGy cm2, for levels A, B, C, and D, respectively. The number of cinegraphic frames ranged within 168 to 182 per case. Our results show that during catheterization interventionalists should vary image intensifier entrance dose levels in accordance with documented structure, angulation, and body mass index. With the exception of cases with special requirements, lower dose levels typically guarantee an adequate image quality.