Intra-articular blockade of P2X7 receptor reduces the articular hyperalgesia and inflammation in the knee joint synovitis especially in female rats

Synovitis is a key factor in joint diseases pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines TNF-α, IL-1β, IL-6 and CINC-1 and by neutrophil migration, was quantified by ELISA and by myeloperoxidase enzyme activity measurement, respectively.

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Hip fracture in a young sportsman

A 33 year old man presented with pain in the left hip, six weeks after running a marathon. The pain was first noticed three weeks before the race. Twenty miles into the race his hip “collapsed”...

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Valence and arousal value of visual stimuli and their role in the mitigation of chronic pain: What is the power of pictures?

The present study investigated the pain-reducing effects of various pictures in a sample of 88 patients receiving inpatient treatment for chronic pain. We investigated whether the pain attenuating effects of the pictures were mediated by picture valence, arousal or change in subjective social support. The study was carried out over four consecutive days. Patients were presented with photographs of loved ones, strangers, landscapes or optical illusions via digital albums and were asked to rate their pain intensity and their sensory and affective experience of pain immediately before and after viewing the pictures.

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Alpha-range visual and auditory stimulation reduces the perception of pain

Abstract

Background

Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz.

Methods

Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency. We collected verbal pain ratings of laser stimuli from participants following 10 minutes of flashing LED goggle stimulation and 10 minutes of binaural beat stimulation across the alpha range. Alterations in sleepiness, anxiety and negative mood were recorded following each auditory or visual alpha-rhythm stimulation session.

Results

A significant reduction in pain ratings was found after both the visual and the auditory stimulation across all three frequencies compared with the control condition. In the visual group, a significantly larger reduction was recorded following the 10-Hz stimulation than succeeding the 8- and 12-Hz conditions.

Conclusions

This study suggests that a short presentation of auditory and visual stimuli, oscillating in the alpha range, have an analgesic effect on acute laser pain, with the largest effect following the 10-Hz visual stimulation. Pain reductions following stimulation in the alpha range are independent of sleepiness, anxiety, and negative moods.

Significance

This study provides new behavioural evidence showing that visual and auditory entrainment of frequencies in the alpha-wave range can influence the perception of acute pain in humans.

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Basal ganglia dysfunction in complex regional pain syndrome – A valid hypothesis?

Abstract

Complex regional pain syndrome (CRPS) is a poorly understood pain disorder of the limbs. Maladaptive cortical plasticity has been shown to play a major role in its pathophysiological presentation. Recently, there is increasing interest in the role of the basal ganglia (BG), since clinical findings and neuroimaging studies point to possible BG involvement in CRPS. CRPS symptoms are often characterized by movement disorders associated with BG dysfunction. Very frequently, dystonia and tremor are reported and, to a lesser extent, myoclonus. Neuroimaging studies present inconsistent findings concerning altered brain networks and mainly focus on cortical areas. Subcortical contribution to this disorder has so far been neglected. Clinical data presenting BG dysfunction-related movement disorders in CRPS patients raise the hypothesis of BG dysfunction in this syndrome. Moreover, several neuroimaging studies documented abnormalities in the BG and in the frontal, parietal and limbic cortical areas. These regions are functionally and anatomically connected in motor, pain and working memory networks. Put together, these findings call for further characterization of the dynamic cortical and subcortical interactions in CRPS.

Significance

This paper presents an overview of our current knowledge about BG pathology in CRPS. A better understanding of the involvement of the BG in the CRPS pathology holds the potential for developing and improving efficacious, mechanism-based treatment modalities.

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Vendor-derived differences in injury-induced pain phenotype and pharmacology of Sprague–Dawley rats: Does it matter?

Abstract

Background

Outbred Sprague–Dawley (SD) rats are a commonly used strain in preclinical pain research. Here, we established empirically how SD rats obtained from different vendors might vary in sensitivity to injury and pharmacotherapy.

Methods

Chronic Constriction Injury (CCI) or complete Freund's adjuvant (CFA) hindpaw inflammation was induced in male SD rats sourced from three to four different vendors, respectively. Neuropathic hypersensitivity was evaluated over 58 days using von Frey filaments, pinprick stimulation and the hot plate test. Pharmacological sensitivity was evaluated by treatment with gabapentin (100 mg/kg, p.o.) or morphine (3 mg/kg, s.c.). CFA-induced hyperalgesia and sensitivity to morphine (0.3–6 mg/kg, s.c.) was measured using a digital Randall–Selitto device. In addition, paw weight gain was used as an index of peripheral oedema.

Results

Significant differences between the vendor-supplied SD rats in relation to onset, magnitude and resolution of hypersensitivity after CCI were observed. Although all sub-strains eventually developed a robust and reversible neuropathic hypersensitivity to mechanical stimulation, the thermal hypersensitivity varied. Whereas pharmacological response to gabapentin varied enormously, the response to morphine was both robust and much more consistent between sub-strains. Despite a similar degree of CFA-induced hypersensitivity, the paw oedema level differed between sub-strains. Here, morphine dose-dependently alleviated the CFA-induced hypersensitivity, with only a subtle difference in sensitivity between sub-strains observed.

Conclusions

Our data reveal that the source of vendor used to obtain SD rats may be one key factor responsible for ‘between laboratory variation’ in reproducing sensitivity to some drugs targeting various pathophysiological mechanisms in specific animal pain models.

Significance

The choice of vendor used to source the same strain of rat for use in preclinical pain research can profoundly affect the level of nociceptive hypersensitivity and response to reference analgesics in neuropathic versus inflammatory models.

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Clinical prediction rules for prognosis and treatment prescription in neck pain: A systematic review

Clinical prediction rules (CPRs) developed to identify sub-groups of people with neck pain for different prognoses (i.e. prognostic) or response to treatments (i.e. prescriptive) have been recommended as a research priority to improve health outcomes for these conditions. A systematic review was undertaken to identify prognostic and prescriptive CPRs relevant to the conservative management of adults with neck pain and to appraise stage of development, quality and readiness for clinical application.

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