Accepted

Knee osteoarthritis (KOA) is a common chronic debilitating disease with an estimated prevalence of 23.9% in the general adult population. The condition is characterised by joint pain, functional impairment and significant reduction in quality of life. Management for KOA can generally be divided into conservative (non-operative) and surgical (operative) measures. Conservative management broadly compromises pharmacological and non-pharmacological options and is conventionally the first line treatment to avoid or delay the need for surgical management. The aim of this study is to provide an overview of the current recommendations, efficacy and safety profile of different conservative treatments through a review of the literature.

Pain is an unpleasant sensation associated with injury, inflammation, and infection. It has been demonstrated that communication between immune cells and neurons plays a vital role in pain and pain-related diseases (e.g. multiple sclerosis, osteoarthritis, irritable bowel syndrome). Growing data from preclinical and clinical studies have established that the bilateral regulations between peripheral immune cells and nociceptive neurons could be beneficial or detrimental for the development of pain and immune defense. We here review the mechanisms underlying neuroimmune crosstalk between circulating immune cells (e.g. macrophages, T cells, mast cells, neutrophils, monocytes) and nociceptors in the peripheral nervous system and the spinal cord. Deciphering the mechanisms by which neuroimmune interaction integrates neuronal inputs and immune responses helps to understand the pathogenesis of pain-related diseases and develop effective medications.

To determine whether glibenclamide, a non-selective adenosine 5'-triphosphate-sensitive K (K) channel blocker, attenuates pituitary adenylate cyclase-activating polypeptide-38 (PACAP38)-induced headache and vascular changes in healthy volunteers.

Exposure to aversive stimuli such as stress results in profound analgesia named stress-induced analgesia (SIA). We previously showed that D1- and D2-like dopamine receptors within the nucleus accumbens (NAc) mediated the SIA in chronic pain. Since the neurophysiological mechanisms responsible for the various pain conditions are different, the present study aimed to examine the role of dopamine receptors within the NAc in the forced swim stress (FSS)-induced analgesia in the tail-flick test as an animal model of acute pain. Ninety-six adult male Wistar rats weighing 200-230 g were unilaterally implanted with a cannula into the NAc. SCH23390 or Sulpiride (0.25, 1, and 4 μg/0.5 μl vehicle), as D1- and D2-like dopamine receptor antagonists, respectively, were microinjected into the NAc, 5 min before exposure to FSS. The vehicle groups received saline or DMSO instead of SCH23390 or Sulpiride, respectively. The tail-flick test was performed in time set intervals after animals were subjected to FSS. The results showed that FSS produces analgesia during the tail-flick test. However, intra-accumbal injection of SCH23390 or Sulpiride attenuated the FSS-induced analgesia. D1-and D2-like dopamine receptor antagonists contributed almost equally to attenuating the antinociceptive responses induced by FSS. It seems that the mesolimbic dopamine system might act as a potential endogenous pain control system in stress conditions. Besides, an improved understanding of this endogenous pain inhibitory system can develop pharmacological and psychological approaches to treat pain.