Little is known about the frequency and impact of the persistent headache and about the incidence of chronic daily headache (CDH) after coronavirus disease 2019 (COVID-19). The aim of this prospective cohort study was to assess the incidence, risk factors, characteristics, and impact of CDH in patients with COVID-19. In the first stage, 288 patients were interviewed by telephone after the acute phase of COVID-19. Subsequently, 199 patients who presented headache were reinterviewed at least one year after COVID-19. Headaches that persisted beyond the acute phase of COVID-19 for three or more months and presented frequency ≥ 45 days over the first three months were considered to be CDH. One hundred and twenty-three patients were included, 56% were females; median age: 50 years (25th and 75th percentile: 41;58). The headache persisted beyond the acute phase of COVID-19 in 52%, and 20.3% had CDH (95% confidence interval: 13.6-28.2). Individuals who previously had headaches and who had headaches of greater intensity during the acute phase were at higher risk of developing CDH. The group with CDH included more females, greater impact of headache, more persistence of headache beyond the 120th day of COVID-19 and less throbbing headache than did the other individuals whose headache persisted. Patients who had COVID-19 had a high incidence of CDH. Previous headache and greater intensity of headache were associated with higher risk of CDH.

Cervical epidural block (CEB) is an effective intervention for managing cervical radicular pain. This study aimed to investigate the current status of performing CEB in South Korea. Pain physicians affiliated with the Korean Pain Society were asked to complete anonymous questionnaires regarding CEB between September and October 2022. The questionnaire consisted of 24 questions assessing the current status and methods of CEB in detail. Of the 198 surveys collected, 171 physicians (86.4%) reported performing CEB. Among those, the majority (94.7%) used fluoroscopy during the procedure. The paramedian interlaminar (IL) approach was the most preferred method (50.3%). Respondents performing fluoroscopic-guided IL CEB were categorized into two groups based on clinical experience: those with ≤10 years of experience (≤10-year group, n = 91) and those with >10 years of experience (>10-year group, n = 71). The proportion of physicians obtaining informed consent in the ≤10-year group and >10-year group was 50.5% and 56.3%, respectively. When entering the epidural space during IL CEB, the contralateral oblique view was the second most frequently used in both groups (≤10-year group, 42.9%; >10-year group, 29.6%). In targeting the upper cervical lesions (C3-4), the proportion of respondents who used an IL space higher than C6-7 was 17.6% in the ≤10-year group and 29.5% in the >10-year experience group. This study demonstrated variability in the CEB technique used by pain physicians in South Korea. The findings highlight the need for education on informed consent and techniques to enhance safety.

Radiofrequency ablation is an effective treatment modality in the symptomatic treatment of knee osteoarthritis. Our aim was to compare the efficacy of radiofrequency ablation of the superomedial and inferomedial genicular nerves (2 branches) with the superolateral, superomedial, and inferomedial genicular nerves (3 branches) and to show whether the 2-branch procedure is inferior to the 3-branch procedure. This study is a prospective, randomized, single-blind clinical study. Eligible participants were randomized into 2 groups: group A, which applied the procedure to the superomedial and inferomedial genicular nerves, and group B, which applied it to the superomedial, superolateral and inferomedial genicular nerves. Pain was evaluated with the numerical rating scale, quality of life with the Short Form-36 (SF-36), and disability with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index before, and at 1 and 3 months after the procedure. A total of 41 patients were included. There were no differences between the groups except for the SF-36 physical health sub-score at baseline. A significant improvement was seen in the numeric rating scale (NRS) score, SF-36 sub-scores, WOMAC Index total, as well as pain and physical function scores in both groups, though no significant difference was detected between the groups during follow-up. Although we were unable to establish the noninferiority of conventional radiofrequency ablation (CRFA) applied to 2 branches to CRFA applied to 3 branches, in this trial, significant and similar improvement was observed in NRS, WOMAC total, pain, and physical function and SF-36 scores in both groups.

Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine HH1-receptor antagonist, 20 mg/kg), cimetidine (histamine H2-receptor antagonist, 12.5 mg/kg), flumazenil (GABAA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systis implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted iploying 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS riained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC50) of HECS was 161.32 ± 0.03 μg/mL. HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

The application of ultrasound (US) in pain medicine has been a rapidly growing field since the 2000s. Musculoskeletal injections, peripheral nerve blocks, and neuraxial injections under US guidance have been acknowledged for managing chronic pain. Although many studies on US-guided pain procedures have been published, there needs to be a classification system to evaluate which image device, the US or fluoroscopy, is clinically and technically better in various pain interventions. Therefore, this narrative review introduces the classification system for the US-guided pain procedures according to their clinical and technical outcomes and designates US-guided pain procedures into one of the four categories by reviewing previous prospective randomized comparative trials.

Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.