Factors Associated with Intermittent, Constant, and Mixed Pain in People with Knee Osteoarthritis

Purpose: To explore factors associated with intermittent, constant, and mixed pain in people with knee osteoarthritis. Method: We conducted a secondary analysis of a cross-sectional multicenter study with adults ≥ 40 years with knee osteoarthritis. Participants completed questionnaires on personal (e.g., demographics, comorbidities), physical (e.g., physical function), psychological (e.g., depressive symptoms), pain (e.g., qualities), and tests for physical performance and nervous system sensitivity. We qualified patients’ pain as intermittent, constant, or mixed using the Modified painDETECT Questionnaire and assessed associations with the variables using multinomial logistic regression. Results: The 279 participants had an average age of 63.8 years (SD = 9.6), BMI of 31.5 kg/m2 (SD = 8.7), and 58.6% were female. Older age (odds ratio [OR] 0.95; 95% CI: 0.90, 1.00) and higher self-reported physical function ([OR] 0.94; 95% CI: 0.91, 0.98) were associated with a lower likelihood of mixed pain compared with intermittent pain. Higher pain intensity ([OR] 1.25; 95% CI: 1.07, 1.47) was related to a 25% higher likelihood of mixed pain compared with intermittent pain. Conclusions: This study provides initial data for associations of personal, pain, and physical function factors with different pain patterns. Awareness of these factors can help clinicians develop targeted strategies for managing patients’ pain.

Semidirect targeting–based stereotactic mesencephalotomy for the treatment of refractory pain: a case series

OBJECTIVE One of the few resources for treating medically intractable pain is ablative surgery, but its indications have fallen dramatically over the last decades. One such procedure is mesencephalotomy. This study aims to determine current risks and benefits of MR-guided semidirect targeting–based stereotactic mesencephalotomy. METHODS This was a retrospective study based on a review of the medical records of 22 patients with nociceptive (n = 5), neuropathic (n = 10), or mixed (n = 7) refractory pain treated with unilateral mesencephalotomy alone (17 patients) or associated with bilateral anterior cingulotomy (5 patients) between 2014 and 2021 in the authors’ institutions. The confidence interval adopted in this study was 95%. RESULTS The sample included 12 women and 10 men with ages ranging from 23 to 80 years (mean 55.1 ± 17.1 years). Using MR-guided semidirect targeting, the following structures were targeted: spinoreticulothalamic (neuropathic/mixed pain, n = 17), trigeminothalamic (nociceptive/mixed pain in the face, n = 5), and neospinothalamic (nociceptive/mixed pain in the body, n = 7) pathways. The most common response to macrostimulation was central heat/moderate discomfort. Radiofrequency thermocoagulation was made with 70°C–75°C/60 sec. A total of 86.3% (3 months) and 76.9% (12 months) of the patients achieved excellent or good results (improvement of pain > 50%), presenting with a significant mean pain relief of 80.1% at 3 months and 71.4% at 12 months postoperatively. The addition of bilateral anterior cingulotomy did not improve the results. Patients with upper limb, cervicobrachial, and face pain did significantly better than those with trunk pain. The worst results were seen in patients with neuropathic and/or trunk pain. The surgical failure (pain relief ≤ 25%) and recurrence rates were 9.1% each, apparently related to the use of lower lesioning parameters (70°C/60 sec) and to the presence of neuropathic and/or trunk pain. The morbidity rate was 8%, with both complications (vertical diplopia and confusion/agitation) happening in patients lesioned with 75°C/60 sec. There were no deaths in this series. CONCLUSIONS These results show that contemporary stereotactic mesencephalotomy is an effective, relatively low-risk, and probably underused procedure for treating medically intractable pain. Careful semidirect determination of the target coordinates associated with close attention to electrical macrostimulation responses certainly plays an important role in avoiding complications in most of the procedures. A higher lesioning temperature (75°C) apparently prevents recurrence, but at the cost of an increased risk of complications.

Opioidrotation bei „mixed pain“ in der Tumorschmerztherapie

ZusammenfassungIm vorliegenden Fallbericht wird die Situation einer 67-jährigen chronischen Schmerzpatientin geschildert, die aufgrund eines Zufallsbefundes mit der Diagnose eines metastasierten kleinzelligen Bronchialkarzinoms konfrontiert wird. Bisher hatte sie mit einer chronischen Lumboischialgie zu kämpfen. Im Verlauf traten zunehmend therapieresistente Tumorschmerzen in den Vordergrund. Es wird beschrieben, wie wichtig es ist, die veränderte Schmerzqualität zu erkennen. Der Tumorschmerz mit neuropathischer Komponente beziehungsweise „mixed pain“ erschwerte im vorliegenden Fallbeispiel eine zufriedenstellende Symptomkontrolle. Es erfolgte ein Wechsel von transdermal appliziertem Fentanyl zu einem subkutanen Perfusorsystem mit Morphin und kurz darauf, aufgrund fehlender Schmerzkontrolle, auf ein orales retardiertes Oxycodonpräparat. Diese zweifache Opioidrotation wird im Folgenden diskutiert. Aspekte wie Resistenzentwicklung, inkomplette Kreuztoleranz und genetische Polymorphismen werden mithilfe wissenschaftlicher Literaturrecherche beleuchtet.

Percutaneous Electrical Nerve Stimulation (PENS) as a Rehabilitation Approach for Reducing Mixed Chronic Pain in Patients with Musculoskeletal Disorders

“Mixed pain” is a term recently introduced to define the overlapping of nociceptive, neuropathic and nociplastic pain. To date, it has been reported that pharmacological treatments might have a modest effectiveness on patients affected by mixed chronic pain, with detrimental consequences in terms of disability, physical function and health-related quality of life. In this scenario, Percutaneous Electrical Nerve Stimulation (PENS), a mini-invasive neuromodulation technique, has been recently suggested as a promising approach for the complex management of mixed pain in musculoskeletal disorders. Albeit PENS showed to be effective in reducing unspecified pain in several chronic pain conditions, there is still a lack of evidence in the literature about its role in the management of neuropathic or mixed pain not responsive to pharmacological treatments. Therefore, by the present scoping review, we portray the potential effects of PENS in the multidisciplinary and multidimensional management of mixed chronic pain in patients with musculoskeletal disorders.

Phosphoproteomic Profiling of Rat’s Dorsal Root Ganglia Reveals mTOR as a Potential Target in Bone Cancer Pain and Electro-Acupuncture’s Analgesia

Bone cancer pain (BCP) is a clinical refractory mixed pain involving neuropathic and inflammatory pain, with the underlying mechanisms remaining largely unknown. Electro-acupuncture (EA) can partly alleviate BCP according to previous research. We aim to explore the proteins and major pathways involved in BCP and EA treatment through phosphoproteomic profiling. BCP rat model was built by tibial inoculation of MRMT-1 mammary gland carcinoma cells. Mechanical hyperalgesia determined by paw withdrawal thresholds (PWTs) and bone destruction manifested on the radiographs confirmed the success of modeling, which were attenuated by EA treatment. The differentially expressed phosphorylated proteins (DEPs) co-regulated by BCP modeling and EA treatment in rat dorsal root ganglions (DRGs) were analyzed through PEX100 Protein microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEPs were significantly enriched in mammalian target of rapamycin (mTOR) signaling pathway. The phosphorylations of mTOR at Ser2448 and Thr2446 were increased in BCP and downregulated by EA. In addition, the phosphorylation of S6K and Akt, markers of the mTOR complex, were also increased in BCP and downregulated by EA. Inhibition of mTOR signaling alleviated the PWTs of BCP rats, while the mTOR agonist impaired the analgesic effect of EA. Thus, our study provided a landscape of protein phosphorylation changes in DRGs of EA-treated BCP rats and revealed that mTOR signaling can be potentially targeted to alleviate BCP by EA treatment.

Diagnosis and Treatment of Chronic Neuropathic and Mixed Pain in Children and Adolescents: Results of a Survey Study amongst Practitioners

Validated diagnostic tools to diagnose chronic neuropathic and mixed pain in children are missing. Therapeutic options are often derived from therapeutics for adults. To investigate the international practice amongst practitioners for the diagnosis and treatment of chronic, neuropathic pain in children and adolescents, we performed a survey study among members of learned societies or groups whose members are known to treat pediatric pain. The survey included questions concerning practitioners and practice characteristics, assessment and diagnosis, treatment and medication. We analyzed 117 returned questionnaires, of which 41 (35%) were fully completed and 76 (65%) were partially completed. Most respondents based the diagnosis of neuropathic pain on physical examination (68 (58.1%)), patient history (67 (57.3%)), and underlying disease (59 (50.4%)) combined. Gabapentin, amitriptyline, and pregabalin were the first-choice treatments for moderate neuropathic pain. Tramadol, ibuprofen, amitriptyline, and paracetamol were the first-choice treatments for moderate mixed pain. Consensus on the diagnostic process of neuropathic pain in children and adolescents is lacking. Drug treatment varies widely for moderate, severe neuropathic, and mixed pain. Hence, diagnostic tools and therapy need to be harmonized and validated for use in children.

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1β, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA.

Assessment of all-cause and cardiovascular death risk in Russian men with leg pain

Aim. To study the prevalence of intermittent claudication (IC) and assess the risk of cardiovascular and all-cause death In Russian men with IC according to 30-year follow-up.Material and methods. The study used data obtained from representative samples of men examined inMoscow andSt. Petersburg (formerly known as Leningrad) from 1975 to 1986. Response rate was 75%. The examination of men (n=10953) aged 35-70 years (mean age 48,8±6,6 years) was carried out according to a single protocol, which included a standard survey, biochemical profile test, measurement of blood pressure (BP) and heart rate, anthropometry and 12-lead electrocardiography. To determine IC, the original Rose questionnaire was used, according to which four categories of pain were identified. The first is the absence of pain (P0); the second — mixed pain, including not associated with exercise (P1); the third — atypical pain in calf muscles lasting >10 minutes of rest (P2); the fourth — typical IC (P3). The median follow-up was 21,9 years. In total, 7,893 people died, including 4220 people due to cardiovascular diseases (CVD). The KaplanMeier curves was used to assess the associations between IC categories and survival. The risk of death, including due to CVD, was assessed using Cox proportional hazard models.Results. There were 38,8% of men with leg pain. The prevalence of IC in the studied sample was 1,0%, increasing with age from 0,4 to 2,3% in the older age group. As expected, individuals without leg pain live the longest. The years of life lost in persons with IC was 12. This parameter for cardiovascular deaths was 22,4 years. The contribution to survival not only of IC (P3), but also of atypical pain (P2) remains significant regardless of age. Moreover, the results of multivariate analysis showed that the contribution to mortality of P3 and P2 does not depend on increased blood pressure, smoking, ischemic and other electrocardiographic abnormalities, a history of myocardial infarction, which indicates the common etiology of lower limb and heart artery diseases. Similar data were obtained regarding cardiovascular mortality, however, the contribution of CI is more significant.Conclusion. IC In Russian men aged 35-70 years is an independent predictor of all-cause and cardiovascular death.