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Offset analgesia describes the effect of a slightly reduced nociceptive stimulus, resulting in a disproportionate large reduction in the pain perception. This effect may be associated with descending pain inhibition, but parameters influencing this phenomenon are poorly understood.

Sex-related influences represent a contributor to greater pain sensitivity and have a higher prevalence of many chronic pain conditions, including neuropathic pain (NP), among women.

Psoriasis is a common, chronic immune-mediated skin disease frequently associated to inflammatory and metabolic comorbidities. About 20-30% of patients are affected by moderate-to-severe psoriasis and require a systemic treatment, which include traditional and biological drugs. The objective of this manuscript is to provide criteria for a personalized biological treatment.

Stellate ganglion block (SGB) is a kind of sympathetic regulator in clinic, which has therapeutic and protective effects on a few central nervous system (CNS) diseases. This study aimed to investigate effect of SGB on nociception in Parkinson disease (PD) rat models and clarify the associated mechanism.

Migraine is thought to involve sensitization of the trigeminal nociceptive system. In preclinical pain models, activation of MNK-eIF4E signaling contributes to nociceptor sensitization and the development of persistent pain. Despite these observations, the role of MNK signaling in migraine remains unclear. Here, we investigate whether activation of MNK contributes to hypersensitivity in two rodent models of migraine. Female and male wild-type (WT) and MNK1 knock-out (KO) mice were subjected to repeated restraint stress or a dural injection of interleukin-6 (IL-6) and tested for periorbital hypersensitivity and grimacing. Upon returning to baseline thresholds, stressed mice were administered a low dose of the nitric oxide donor sodium nitroprusside (SNP) and mice previously injected with IL-6 were given a second dural injection of pH 7.0 to test for hyperalgesic priming. MNK1 KO mice were significantly less hypersensitive than WTs following dural IL-6 and did not prime to pH 7.0 or SNP. Furthermore, treatment with the selective MNK inhibitor, eFT508, in WT mice prevented hypersensitivity caused by dural IL-6 or pH 7.0. Together, these results implicate MNK-eIF4E signaling in the development of pain originating from the dura and strongly suggest that targeting MNK inhibition may have significant therapeutic potential as a treatment for migraine.

Evidence-based pain therapy should rely on precisely defined and personalized criteria. This includes balancing the benefits and risks not only of single drugs but often requires complex between-drug comparisons. Non-steroidal anti-inflammatory drugs (NSAIDs) have been available for several decades and their use is described in an abundance of guidelines. Most of these guidelines recommend that 'the selection of a particular NSAID should be based on the benefit-risk balance for each patient'. However, head-to-head studies are often lacking or of poor quality, reflecting the lower standards for clinical research and regulatory approval at the time. The inconsistency of approved indications between countries due to national applications adds to the complexity. Finally, a fading research interest once drugs become generic points to a general deficit in the post-marketing evaluation of medicines. Far from claiming completeness, this narrative review aimed to illustrate the challenges that physicians encounter when trying to balance benefits and risks in a situation of incomplete and inconsistent data on longstanding treatment concepts. Ibuprofen and mefenamic acid, the most frequently sold NSAIDs in Austria, serve as examples. The illustrated principles are, however, not specific to these drugs and are generalizable to any comparison of older drugs in daily clinical practice.

(1) : The aim of this narrative review was to analyze the neuroanatomical and neurophysiological basis of cervicogenic pain in cervico-cranial pain syndromes, focusing particularly on cervico-orofacial syndromes as a background for the proper diagnosis and non-surgical treatment. Relevant literature on the topic from past 120 years has been surveyed. (2) : We surveyed all original papers, reviews, or short communications published in the English, Spanish, Czech or Slovak languages from 1900 to 2020 in major journals. (3) : The cervicogenic headache originates from the spinal trigeminal nucleus where axons from the C-C cervical spinal nerves and three branches of the trigeminal nerve converge (trigeminocervical convergence) at the interneurons that mediate cranio-cervical nociceptive interactions. The role of the temporomandibular joint in the broad clinical picture is also important. Despite abundant available experimental and clinical data, cervicogenic orofacial pain may be challenging to diagnose and treat. Crucial non-surgical therapeutic approach is the orthopedic manual therapy focused on correction of body posture, proper alignment of cervical vertebra and restoration of normal function of temporomandibular joint and occlusion. In addition, two novel concepts for the functional synthesis of cervico-cranial interactions are the tricentric concept of mouth sensorimotor control and the concept of a cervicogenic origin of bruxism. (4) : Understanding the basis of neuroanatomical and neurophysiological neuromuscular relations enables an effective therapeutic approach based principally on orthopedic manual and dental occlusal treatment.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. A total of 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 min-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with two control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed. Reduced BRS in FM at baseline increased by 41% during two, ≈8 min-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps < 0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations ( < 0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic responses.

Opioid-induced hyperalgesia (OIH) is a paradoxical effect of opioids that is not consensually recognized in clinical settings. We conducted a revision of clinical and preclinical studies and discuss them side by side to provide an updated and renewed view on OIH. We critically analyze data on the human manifestations of OIH in the context of chronic and post-operative pain. We also discuss how, in the context of cancer pain, though there are no direct evidence of OIH, several inherent conditions to the tumor and chemotherapy provide a substrate for the development of OIH. The review of the clinical data, namely in what concerns the strategies to counter OIH, emphasizes how much OIH rely mechanistically on the existence of µ-opioid receptor (MOR) signaling through opposite, inhibitory/antinociceptive and excitatory/pronociceptive, pathways. The rationale for the maladaptive excitatory signaling of opioids is provided by the emerging growing information on the functional role of alternative splicing and heteromerization of MOR. The crossroads between opioids and neuroinflammation also play a major role in OIH. The latest pre-clinical data in this field brings new insights to new and promising therapeutic targets to address OIH. In conclusion, although OIH remains insufficiently recognized in clinical practice, the appropriate diagnosis can turn it into a treatable pain disorder. Therefore, in times of scarce alternatives to opioids to treat pain, mainly unmanageable chronic pain, increased knowledge and recognition of OIH, likely represent the first steps towards safer and efficient use of opioids as analgesics.

We present a narrative review focusing on the new role of nociception monitor in intraoperative anesthetic management. Higher invasiveness of surgery elicits a higher degree of surgical stress responses including neuroendocrine-metabolic and inflammatory-immune responses, which are associated with the occurrence of major postoperative complications. Conversely, anesthetic management mitigates these responses. Furthermore, improper attenuation of nociceptive input and related autonomic effects may induce increased stress response that may adversely influence outcome even in minimally invasive surgeries. The original role of nociception monitor, which is to assess a balance between nociception caused by surgical trauma and anti-nociception due to anesthesia, may allow an assessment of surgical stress response. The goal of this review is to inform healthcare professionals providing anesthetic management that nociception monitors may provide intraoperative data associated with surgical stress responses, and to inspire new research into the effects of nociception monitor-guided anesthesia on postoperative complications.