Accepted

Platelets are an essential component of hemostasis, with an increasing role in host inflammatory processes in injured tissues. The reaction between receptors and vascular endothelial cells results in the recruitment of platelets in the immune response pathway. The aim of the present review is to describe the role of platelets in osteoarthritis. Platelets induce secretion of biological substances, many of which are key players in the inflammatory response in osteoarthritis. Molecules involved in cartilage degeneration, or being markers of inflammation in osteoarthritis, are cytokines, such as tumor necrosis factor α (TNFα), interleukins (IL), type II collagen, aggrecan, and metalloproteinases. Surprisingly, platelets may also be used as a treatment modality for osteoarthritis. Multiple randomized controlled trials included in our systematic review and meta-analyses prove the effectiveness of platelet-rich plasma (PRP) as a minimally invasive method of pain alleviation in osteoarthritis treatment.

Patients with chronic pain, especially orofacial pain, often suffer from affective disorders, including anxiety. Previous studies largely focused on the role of the caudal anterior cingulate cortex (cACC) in affective responses to pain, long-term potentiation (LTP) in cACC being thought to mediate the interaction between anxiety and chronic pain. But recent evidence indicates that the rostral ACC (rACC), too, is implicated in processing affective pain. However, whether such processing is associated with neuronal and/or synaptic plasticity is still unknown. We addressed this issue in a chronic facial inflammatory pain model (complete Freund's adjuvant model) in rats, by combining behavior, Fos protein immunochemistry and ex vivo intracellular recordings in rACC slices prepared from these animals. Facial mechanical allodynia occurs immediately after CFA injection, peaks at post-injection day 3 and progressively recovers until post-injection days 10-11, whereas anxiety is delayed, being present at post-injection day 10, when sensory hypersensitivity is relieved, but, notably, not at post-injection day 3. Fos expression reveals that neuronal activity follows a bi-phasic time course in bilateral rACC: first enhanced at post-injection day 3, it gets strongly depressed at post-injection day 10. Ex vivo recordings from lamina V pyramidal neurons, the rACC projecting neurons, show that both their intrinsic excitability and excitatory synaptic inputs have undergone long-term depression (LTD) at post-injection day 10. Thus chronic pain processing is associated with dynamic changes in rACC activity: first enhanced and subsequently decreased, at the time of anxiety-like behavior. Chronic pain-induced anxiety might thus result from a rACC deactivation-cACC hyperactivation interplay.

Success rates of spinal surgeries to treat chronic back pain are highly variable and useable prognostic indicators are lacking. We aimed to identify and evaluate preoperative predictors of pain and disability after spinal surgery for chronic low back/leg pain.

Neck pain is a common musculoskeletal problem often accompanied by reduced exercise-induced hypoalgesia (EIH) or hyperalgesia compared to an asymptomatic population. This study investigated EIH in a healthy population during experimental neck pain. Forty participants were randomized into this double-blinded parallel-group study. On four separate test days (Day0, Day2, Day4, Day15), participants completed the Neck Disability Index (NDI) and scored neck pain intensity during head movements on a numerical rating scale (NRS). At the end of Day0 and Day2, Nerve Growth Factor (NGF) or isotonic saline (control) was injected into the right splenius capitis muscle. Pressure pain thresholds (PPTs) were recorded bilaterally over splenius capitis (neck), temporalis (head) and tibialis anterior (leg) muscles on all days. On Day0, Day4 and Day15, PPTs were recorded before and after a hand-bike exercise. EIH was defined as the PPT increase caused by the exercise. Compared with the control-group, the NGF-group demonstrated higher NDI scores at Day2 and Day4 (P<0.001,η2>0.557) and higher NRS scores (P<0.03,η2>0.09) along with reduced neck PPTs (P<0.01,d>0.44) at Day2(Right:95%CI[26.0,54.0];Left:95%CI[6.8,26.9]), Day4(Right:95%CI[40.5, 67.9];Left:95%CI[6.9,28.2]) and Day15(Right:95%CI[5.6,37.2];Left:95%CI[6.9,34.8]). Across days, the EIH-effect was reduced at the neck site in the NGF-group compared to the control-group (P<0.001,η2P=0.367,95%CI[-34.5,-13.7]). At the head and leg sites, the NGF-group showed reduced EIH-effect compared to the control-group (P<0.05,d>0.43) on Day4(Head:95%CI[-61.4,-22.9];Leg:95%CI[-154.7,-72.4]) and Day15(Head:95%CI[-54.3,-7.6];Leg:95%CI[-122.7,-34.4]). These results indicate that a few days of clinically comparable neck pain and hyperalgesia might have a negative impact on EIH-responses and may help explain why some neck pain patients do not experience immediate positive effects of exercise.