clozapine and Chronic-Pain

Social inequality in medical rehabilitation is receiving increasing attention. The present study examined the impact of the social status on the long-term effectiveness of the pain competence and depression prevention training "Debora" among patients with chronic low back pain (CLBP) in an inpatient multidisciplinary rehabilitation.. In general, patients of the lower class showed significantly worse values in depressive symptoms, functional capacity, and subjective work ability compared to the upper class. In addition, positive long-term effects could not be found among patients of the lower class. In contrast, patients of the middle and upper class improved, especially in the IG. Furthermore, only the IG showed long-term improvements in subjective work capacity.. This study confirms the influence of the social status on the psychophysical health. Moreover, social inequality in long-term success of rehabilitation of CLBP was suggested, which could be mediated by health literacy. Therefore, these aspects should be taken into account already in the conception and especially in the application of psychological group trainings in inpatient rehabilitation.. Die soziale Ungleichheit in der medizinischen Rehabilitation findet zunehmend Beachtung. Die vorliegende Studie untersuchte die langfristige Wirksamkeit des Schmerzkompetenz- und Depressionspräventionstrainings Debora bei Rehabilitanden mit chronischen Rückenschmerzen in der stationären verhaltensmedizinisch orthopädischen Rehabilitation (VMO) in Abhängigkeit von der sozialen Lage.. Rehabilitanden der Unterschicht wiesen in der Depressivität, Funktionskapazität und subjektiven Arbeitsfähigkeit generell signifikant schlechtere Werte im Vergleich zur Oberschicht auf. Zudem blieben positive Langzeiteffekte bei Rehabilitanden der Unterschicht eher aus. Dagegen verbesserten sich Rehabilitanden der Mittel- und Oberschicht insbesondere in der IG. Ferner zeigte sich, dass lediglich die IG langfristig in der subjektiven Arbeitsfähigkeit profitierte.. Die Studie belegt den Einfluss der sozialen Lage auf die psychophysische Gesundheit. Ferner wird eine soziale Ungleichheit im langfristigen Rehabilitationserfolg bei chronischen Rückenschmerzen nahegelegt, die durch die Gesundheitskompetenz vermittelt sein könnte. Somit sollten diese Aspekte bereits bei der Konzeption und insbesondere bei der Durchführung von psychologischen Gruppentrainings in der stationären medizinischen Rehabilitation bei chronischen Rückenschmerzen berücksichtigt werden.

Topics: Age Factors; Antipsychotic Agents; Chronic Pain; Clozapine; Cytochrome P-450 CYP1A2; Female; Follow-Up Studies; Functional Status; Germany; Health Literacy; Humans; Inpatients; Low Back Pain; Male; Patient Care Team; Psychological Distress; Rehabilitation; Return to Work; Schizophrenia; Self Efficacy; Sex Factors; Smoking; Social Class; Treatment Outcome

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABA

Topics: Animals; Anti-Anxiety Agents; Anxiety; Central Nervous System Sensitization; Chronic Pain; Clozapine; Freund's Adjuvant; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; GABAergic Neurons; Genetic Vectors; Gyrus Cinguli; Inflammation; Injections; Interneurons; Male; Muscimol; Open Field Test; Pain Threshold; Patch-Clamp Techniques; Picrotoxin; Presynaptic Terminals; Pyramidal Cells; Rats; Rats, Sprague-Dawley

Opioid use for pain management has dramatically increased, with little assessment of potential pathophysiological consequences for the primary pain condition. Here, a short course of morphine, starting 10 d after injury in male rats, paradoxically and remarkably doubled the duration of chronic constriction injury (CCI)-allodynia, months after morphine ceased. No such effect of opioids on neuropathic pain has previously been reported. Using pharmacologic and genetic approaches, we discovered that the initiation and maintenance of this multimonth prolongation of neuropathic pain was mediated by a previously unidentified mechanism for spinal cord and pain-namely, morphine-induced spinal NOD-like receptor protein 3 (NLRP3) inflammasomes and associated release of interleukin-1β (IL-1β). As spinal dorsal horn microglia expressed this signaling platform, these cells were selectively inhibited in vivo after transfection with a novel Designer Receptor Exclusively Activated by Designer Drugs (DREADD). Multiday treatment with the DREADD-specific ligand clozapine-N-oxide prevented and enduringly reversed morphine-induced persistent sensitization for weeks to months after cessation of clozapine-N-oxide. These data demonstrate both the critical importance of microglia and that maintenance of chronic pain created by early exposure to opioids can be disrupted, resetting pain to normal. These data also provide strong support for the recent "two-hit hypothesis" of microglial priming, leading to exaggerated reactivity after the second challenge, documented here in the context of nerve injury followed by morphine. This study predicts that prolonged pain is an unrealized and clinically concerning consequence of the abundant use of opioids in chronic pain.

Topics: Animals; Chronic Pain; Clozapine; Inflammasomes; Interleukin-1beta; Male; Microglia; Morphine; Neuralgia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Spinal Cord Dorsal Horn