Кукушкин М.Л.-д.м.н., профессор, руководитель лаборатории фундаментальных и прикладных проблем боли ФГБНУ «НИИ общей патологии и патофизиологии» 5 , ответственный секретарь Российского общества по изучению боли,

Melatonin is a neurohormone secreted by epiphysis and extrapineal structures. It performs several functions including chronobiotic, antioxidant, oncostatic, immune modulating, normothermal, and anxiolytic functions. Melatonin affects the cardiovascular system and gastrointestinal tract, participates in reproduction and metabolism, and body mass regulation. Moreover, recent studies have demonstrated melatonin efficacy in relation to pain syndromes. The present paper reviews the studies on melatonin use in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The paper discusses the possible mechanisms of melatonin analgesic properties. On one hand, circadian rhythms normalization results in sleep improvement, which is inevitably disordered in chronic pain syndromes, and activation of melatonin adaptive capabilities. On the other hand, there is evidence of melatonin-independent analgesic effect involving melatonin receptors and several neurotransmitter systems.

SummaryAimsThe aim of this non‐systematic review was to provide a practical guide for clinicians on the evidence for central sensitisation in chronic osteoarthritis (OA) pain and how this pain mechanism can be addressed in terms of clinical diagnosis, investigation and treatment.MethodsThe authors undertook a non‐systematic review of the literature including a MEDLINE search (search terms included central sensitisation, osteoarthritis, osteoarthrosis) for relevant and current clinical studies, systematic reviews and narrative reviews. Case reports, letters to the editor and similar literature sources were excluded. Information was organised to allow a pragmatic approach to the discussion of the evidence and generation of practical recommendations.ResultsThere is good evidence for a role of central sensitisation in chronic OA pain in a subgroup of patients. Clinically, a central sensitisation component in chronic OA pain can be suspected based on characteristic pain features and non‐pain features seen in other conditions involving central sensitisation. However, there are currently no diagnostic inventories for central sensitisation specific to OA. Biomarkers may be helpful for confirming the presence of central sensitisation, especially when there is diagnostic uncertainty. Several non‐pharmacological and pharmacological treatments may be effective in OA patients with central sensitisation features. Multimodal therapy may be required to achieve control of symptoms.DiscussionClinicians should be aware of central sensitisation in patients with chronic OA pain, especially in patients presenting with severe pain with unusual features.

We evaluated the analgesic efficacy, safety and tolerability of a novel chemokine receptor 2 (CCR2) antagonist, AZD2423, in posttraumatic neuralgia. This was a double-blind, randomized, parallel-group, multicentre study. One hundred thirty-three patients with posttraumatic neuralgia were equally randomized to 28days' oral administration of 20mg AZD2423, 150mg AZD2423 or placebo. The primary efficacy variable was the change of average pain score from 5days at baseline to the last 5days of treatment, measured by a numerical rating scale (NRS, 0-10). The secondary efficacy measures included NRS worst pain score, patient global impression of change, pain interference on sleep and activity, and Neuropathic Pain Symptom Inventory (NPSI). The change of the NRS average pain score was not significantly different between treatment groups (AZD2423 20mg -1.54; AZD2423 150mg -1.53; placebo -1.44). There were trends towards larger reduction of NPSI total score and NPSI subscores for paroxysmal pain and paresthesia/dysesthesia by AZD2423 150mg compared to placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. Increased plasma levels of chemokine ligand 2 and reduced mean levels of monocytes (-30% by AZD2423 150mg) suggested that the administrated doses of AZD2423 had interacted with the CCR2 target. The CCR2 antagonist AZD2423 demonstrated no efficacy on NRS average pain scores and most of the secondary pain variables. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns.

To explore the possible involvement of the pain control system, pain pressure threshold (PPT), nociceptive flexion reflex (RIII), blink and corneal reflexes have been studied for pain perception assessment in 12 patients with chronic paroxysmal hemicrania (CPH) and 12 patients with hemicrania continua (HC). PPT was found to be reduced in HC and CPH when separately compared to controls. In addition, a significant reduction of subjective pain perception (Tp) which was most marked on the symptomatic side, has been demonstrated after sural nerve stimulation in CPH. The RIII reflex threshold on the symptomatic side was significantly reduced when patients were compared to controls. No major differences between CPH and HC as regards blink reflex latencies were found; nor was any such difference observed when comparing the two headache groups to controls. The corneal reflex thresholds were found significantly reduced bilaterally in CPH, irrespective of whether the treatment was given or not.

The nociceptive flexion reflex (NFR) of the lower limbs (RIII reflex) was examined bilaterally in 54 cluster headache (CH) patients suffering from episodic CH (ECH) and chronic CH (CCH). Fifteen ECH patients were examined in both remission and active phases. The RIII reflex threshold (Tr) and the threshold of pain sensation (Tp) were significantly reduced on the symptomatic side in patients with episodic CH during the bout. During the active phase of episodic CH an inverse correlation was found between the severity of CH (ratio: number of cluster periods/years of illness duration) and the Tp, which may suggest a role for secondary central sensitization in pain pathways. The lower Tr and Tp on the symptomatic side is in keeping with previous observations exploring pain mechanisms using different methods (i.e. corneal reflex, pain pressure threshold). On the whole, these data tie in with the view of an impairment of the pain control system, which parallels the periodicity of the disorder in the episodic form.

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The review is devoted to the complex relationship between headache and sleep disorders. The shared neuroanatomical structures of the nervous system involved in pain perception and sleep are shown, and mechanisms of comorbidity between headaches and sleep disorders are considered. Various types of headaches in the continuum of the sleep–wake cycle are described. Both pharmacological and non-pharmacological approaches to treatment are examined in detail, with the biochemical basis of the drug action.