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Social support has been shown to reduce pain ratings and physiological responses to acute pain stimuli. Furthermore, this relationship is moderated by adult attachment styles. However, these effects have not been characterized in experimentally induced symptoms of chronic pain, such as secondary hyperalgesia (SH) which is characterized by an increased sensitivity of the skin surrounding an injury. We aimed to examine whether social support by handholding from a romantic partner can attenuate the development of experimentally induced SH. Thirty-seven women, along with their partners, participated in 2 experimental sessions 1 week apart. In both sessions, SH was induced using an electrical stimulation protocol. In the support condition, the partner was seated across from the participant holding the participant’s hand during the electrical stimulation, whereas in the alone condition, the participant went through the stimulation alone. Heart rate variability was measured for both the participant as well as the partner before, during, and after the stimulation. We found that the width of the area of hyperalgesia was significantly smaller in the support condition. Attachment styles did not moderate this effect of social support on the area width. Increasing attachment avoidance was associated with both a smaller width of hyperalgesia and a smaller increase in the sensitivity on the stimulated arm. For the first time, we show that social support can attenuate the development of secondary hyperalgesia and that attachment avoidance may be associated with an attenuated development of secondary hyperalgesia. [ABSTRACT FROM AUTHOR]

In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC. [ABSTRACT FROM AUTHOR]

Abstract: Cutaneous inflammation induced by ultraviolet (UV) irradiation in the UV-B range has received significant recent interest as a translational inflammatory pain model. Changes in thermal and mechanical sensitivities in the area of primary hyperalgesia are well documented in both the rat and human UV-B models, but the occurrence of secondary mechanical hyperalgesia is controversial. We investigated the occurrence of secondary mechanical hyperalgesia in the rat UV-B model. Additionally, we investigated whether secondary hyperalgesia was enhanced by heat rekindling of UV-B-irradiated skin as a new rat inflammatory model of sensitisation with an enhanced central contribution. UV-B irradiation (1000mJ/cm2) induced significant secondary mechanical hyperalgesia and allodynia that peaked at 48h. Heat rekindling (45°C stimulus for 5min) of UV-B-irradiated skin at 24h further enhanced and prolonged this secondary mechanical hyperalgesia and allodynia, with a peak at 72h. Heat rekindling also induced a significant mechanical hyperalgesia and allodynia on the contralateral hind paw, further suggesting the contribution of central sensitisation. Our data provide strong evidence for a central contribution in both the rat UV-B pain model and an enhanced contribution in the new model combining UV-B irradiation with heat rekindling. We also elucidate potential differences in the methods used by ourselves and others to obtain mechanical withdrawal thresholds in rats, which may explain the lack of secondary hyperalgesia in the rat UV-B model. [Copyright &y& Elsevier]

Abstract: Intra-articular injection of Freund’s complete adjuvant (FCA) into the rat knee joint produces a swelling of the joint and long lasting hypersensitivity. In this study we have used this model and in vivo electrophysiology to investigate the timecourse of spinal changes underlying chronic secondary hypersensitivity, by stimulating the ankle joint (an area outside the site of primary hypersensitivity), and have compared the results with behavioural data from the same population of animals at 4–8, 13–17 and 55–59days following FCA injection. The magnitude of responses and the proportion of dorsal horn neurones receiving inputs from Aβ- Aδ- and C-fibre afferents were monitored. At all timepoints, there was a significant increase in the ongoing activity of deep dorsal horn neurones when compared to naı¨ve rats, correlating well with the behavioural hypersensitivity. Both the magnitude of neuronal responses, and the proportion of neurones responding to electrical or mechanical stimulation in an area of secondary hypersensitivity, were significantly increased 4–8 and 13–17days following FCA injection. However, while there was still behavioural hypersensitivity at 55–59days there was a substantial decline in the responses to mechanical stimulation and A-fibre responses to electrical stimulation, although the proportion of neurones responding in the C-fibre latency remained elevated. These results suggest that the behavioural hypersensitivity is due to hyperexcitability at the level of the dorsal horn reflected as an increase of both C-fibre responses and spontaneous activity. [Copyright &y& Elsevier]

Abstract: Animal studies have established a role for the brainstem reticular formation, in particular the rostral ventromedial medulla (RVM), in the development and maintenance of central sensitisation and its clinical manifestation, secondary hyperalgesia. Similar evidence in humans is lacking, as neuroimaging studies have mainly focused on cortical changes. To fully characterise the supraspinal contributions to central sensitisation in humans, we used whole-brain functional magnetic resonance imaging at 3T, to record brain responses to punctate mechanical stimulation in an area of secondary hyperalgesia. We used the heat/capsaicin sensitisation model to induce secondary hyperalgesia on the right lower leg in 12 healthy volunteers. A paired t-test was used to compare activation maps obtained during punctate stimulation of the secondary hyperalgesia area and those recorded during control punctate stimulation (same body site, untreated skin, separate session). The following areas showed significantly increased activation (Z>2.3, corrected P&#60;0.01) during hyperalgesia: contralateral brainstem, cerebellum, bilateral thalamus, contralateral primary and secondary somatosensory cortices, bilateral posterior insula, anterior and posterior cingulate cortices, right middle frontal gyrus and right parietal association cortex. Brainstem activation was localised to two distinct areas of the midbrain reticular formation, in regions consistent with the location of nucleus cuneiformis (NCF) and rostral superior colliculi/periaqueductal gray (SC/PAG). The PAG and the NCF are the major sources of input to the RVM, and therefore in an ideal position to modulate its output. These results suggest that structures in the mesencephalic reticular formation, possibly the NCF and PAG, are involved in central sensitisation in humans. [Copyright &y& Elsevier]

Abstract: This study compares the effect of experimental muscle pain on deep tissue sensitivity and force attenuation in the wrist extensors of patients with lateral epicondylalgia (n=20), and healthy controls (n=20) with experimentally induced sensori-motor characteristics simulating lateral epicondylalgia. Delayed onset muscle soreness (DOMS) in wrist extensors of healthy controls was induced by eccentric exercise in one arm 24h prior to injection (Day 0). Saline-induced pain intensity (visual analogue scale, VAS), distribution, and quality were assessed quantitatively in both arms for both groups. Pressure pain thresholds (PPT) were assessed at three different sites in the wrist extensors. Maximal grip force and wrist extension force were recorded. In response to saline-induced pain in the extensor carpi radialis brevis, regardless of arm, the patient group demonstrated a significantly quicker pain onset (P&#60;0.01), mapped larger pain areas and more referred pain areas, compared to healthy controls (P&#60;0.03). Pain persisted significantly longer in the sore arm of the patient group, compared with all other arms (P&#60;0.02). Patients demonstrated significant bilateral hyperalgesia at extensor carpi radialis brevis during and post saline-induced pain compared to pre-injection and healthy controls (P&#60;0.04). The sore arm in patients and the DOMS arms in healthy subjects showed significantly reduced maximal force (P&#60;0.0001), at all Day 1 times compared with the control arms. In patients, the bilateral increase in deep tissue sensitivity and enlarged referred pain areas during saline-induced pain might suggest involvement of central sensitisation. [Copyright &y& Elsevier]

Pathophysiological processes in the viscera can lead to pain and hyperalgesia and exaggerated motility-regulating reflexes. This may be due to sensitisation of visceral afferents (peripheral sensitisation), which has repeatedly been shown to occur as a consequence of e.g. inflammation, and/or to sensitisation of dorsal horn neurones (central sensitisation), which is less well documented in the visceral domain. As an indicator of peripheral sensitisation, we previously analysed the responses of sacral spinal afferents after inflammation of the urinary bladder. Here, we studied reflexes in sympathetic vasoconstrictor neurones supplying skeletal muscle and skin elicited by bladder distension stimuli (vesico-sympathetic reflexes) before and after induction of bladder inflammation. Our aim was to test whether these vesico-sympathetic reflexes are amplified after inflammation in a way that would support a major functional role for post-inflammatory central sensitisation processes. Bladder inflammation was induced in anaesthetised cats by instillation of turpentine or mustard oil and vesico-sympathetic reflexes were studied 1 and 2 h after induction of the inflammation. Inflammation enhanced on-going activity in vasoconstrictor neurones supplying skeletal muscle (after 1 h to 187.6±36.8%, mean±SEM, P<0.01, and after 2 h to 139.1±12.9%, P<0.05, of baseline activity) and decreased it in most sympathetic neurones supplying skin (to 91.7±12.5%, P>0.05, and to 71.6±11.3%, P<0.05, respectively, of baseline activity). Relative to the altered baseline activity vesico-sympathetic reflexes to graded distension of the inflamed bladder were quantitatively unchanged with a tendency to be diminished. Thus, the changes in on-going sympathetic vasoconstrictor activity and the distension-evoked reflexes directly mirrored the afferent input from the inflamed urinary bladder into the spinal cord, i.e. no increase of the gain of these reflexes was observed. These results suggest that in the first 2 h of inflammation, peripheral sensitisation processes play the main role for hyperalgesia and hyperreflexia of the urinary bladder. In contrast, central sensitisation appears to be of little importance during this time period. [Copyright &y& Elsevier]