Browse by Audience
Our research group recently published a positive association between early postoperative pain and 30-day postoperative complications in a broad surgical population. To investigate whether heterogeneity of the population and surgical procedures influenced these results, we explored this association in a homogenous surgical population. A secondary analysis of the LEOPARD-2 (clinicaltrials.gov NCT02146417) and RELAX-1 study (NCT02838134) in laparoscopic donor nephrectomy patients (n=160) was performed. Pain scores on the post-anesthesia care unit and postoperative day (POD) 1 and 2 were compared between patients with infectious, non-infectious, and no complications 30 days after surgery. Patients who developed infectious complications had significantly higher pain scores on POD1 and 2 (6.7 ± 2.1 and 6.4 ± 2.8) than patients without complications (4.9 ± 2.2 and 4.1 ± 1.9), respectively (p=0.006 and P=0.000). Unacceptable pain (NRS≥6) on POD1 was reported by 72% of patients who developed infectious complications, compared to 38% with non-infectious complications and 30% without complications (p=0.018). This difference was still present on POD2 at 67% with infectious complications, 21% with non-infectious and 40% without complications (P=0.000). Multiple regression analysis identified unacceptable pain (NRS ≥6) on POD2 as a significant predictor for 30-day infectious complications (OR 6.09, P=0.001). Results confirm the association between early postoperative pain and 30-day infectious complications in a separate, homogenous surgical population. Further clinical trials should focus on finetuning of postoperative analgesia to elucidate the effects on the endocrine and immune response, preserve immune homeostasis and prevent postoperative infectious complications.
Learn More >Central post-stroke pain (CPSP) is a type of neuropathic pain for which the mechanism and relevant drug pathways remain unknown. Recently, it was reported that intracerebroventricular (ICV) administration of orexin-A suppresses pain and ischemia. In this study, we tested the role of orexin-A in CPSP induction in mice. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). CPSP was assessed by von Frey test. Colocalization of orexin 1 receptor (OX1R) with various neuron markers were determined by double-immunofluorescence. The hindpaw withdrawal responses to mechanical stimuli were significantly increased 3 days post-BCAO compared with those of sham groups. ICV injection of orexin-A dose-dependently suppressed BCAO-induced mechanical allodynia. These effects were inhibited by pre-treatment with SB334867 (an OX1R antagonist; ICV injection), yohimbine (a noradrenaline α receptor antagonist; intrathecal (IT) injection), and WAY100635 (a serotonin 5-HT receptor antagonist; IT injection), but not TCS OX2 29 (an OX2R antagonist; ICV injection). OX1R colocalized with TH (a noradrenergic neuron marker) and TPH (a serotonergic neuron marker) in the locus ceruleus (LC) and the rostral ventromedial medulla (RVM), respectively. The number of c-Fos positive cells in the LC and the RVM of BCAO mice was increased at 90 min after ICV injection of orexin-A compared to saline group. These results indicate that orexin-A/OX1R signaling plays an important role through activation of the descending pain control system in the induction of CPSP in mice.
Learn More >Visceral hypersensitivity is common in patients with irritable bowel syndrome (IBS). We investigated whether inflammatory molecules, such as histamine and proteases, activate prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) to increase the synthesis of prostaglandin E2 (PGE2) by mast cells, which activates the receptor PTGER2 (also called EP2) in the dorsal root ganglia to promote visceral hypersensitivity.
Learn More >To review qualitative studies on the experience of taking opioid medication for chronic non-malignant pain (CNMP) or coming off them.
Learn More >Myofascial Pain Syndrome (MPS) is one of the most common conditions of chronic musculoskeletal pain, yet its mechanisms are still poorly understood. Delayed Onset Muscle Soreness (DOMS) is also a regional pain syndrome that has clinical similarities to MPS, but has been better investigated. Emerging research suggests that DOMS may be a valid experimental model for studying MPS; however, a comparison of the similarities and differences of these two conditions has previously not been performed. Herein, we aimed to identify the similarities and differences in the clinical features and biomarkers between DOMS and MPS in order to better define MPS and identify future areas of (DOMS-informed) MPS research.
Learn More >Human α-calcitonin gene-related peptide (h-α-CGRP) is a highly potent vasodilator peptide that belongs to the family of calcitonin peptides. There are two forms of CGRP receptors in humans and rodents: α-CGRP receptor predominately found in the cardiovascular system and β-CGRP receptor predominating in the gastrointestinal tract. The CGRP receptors are primarily localized to C and Aδ sensory fibers, where they are involved in nociceptive transmission and migraine pathophysiology. These fibers are found both peripherally and centrally, with extensive perivascular location. The CGRP receptors belong to the class B G-protein-coupled receptors, and they are primarily associated to signaling via Gα proteins. The objectives of the present work were: (i) synthesis of three single-labelled fluorescent analogues of h-α-CGRP by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis, and (ii) testing of their biological activity in isolated human, mouse, and rat arteries by using a small-vessel myograph setup. The three analogues were labelled with 5(6)-carboxyfluorescein via the spacer 6-aminohexanoic acid at the chain of Lys or Lys. Circular dichroism (CD) experiments were performed to obtain information on the secondary structure of these fluorescently labelled peptides. The CD spectra indicated that the folding of all three analogues was similar to that of native α-CGRP. The three fluorescent analogues of α-CGRP were successfully prepared with a purity of >95%. In comparison to α-CGRP, the three analogues exhibited similar efficacy, but different potency in producing a vasodilator effect. The analogue labelled at the N-terminus proved to be the most readily synthesized, but it was found to possess the lowest vasodilator potency. The analogues labelled at Lys or Lys exhibited an acceptable reduction in potency (i.e., 3-5 times and 5-10 times less potent, respectively), and thus they have potential for use in further investigations of receptor internalization and neuronal reuptake.
Learn More >To explore the perspectives of general practitioners (GPs) concerning the risk of opioid misuse in people with cancer and pain and related clinical considerations.
Learn More >Neuropathic low back-related leg pain (LBLP) can be a challenge to healthcare providers to diagnose and treat. Accurate diagnosis of neuropathic pain is fundamental to ensure appropriate intervention is given. However, to date there is no gold standard to diagnose neuropathic LBLP. A Delphi study will therefore be conducted to obtain an expert-derived consensus list of clinical indicators to identify a neuropathic component to LBLP.
Learn More >Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.
Learn More >To investigate the structural and functional connectivity changes of lateral geniculate nucleus (LGN) and their relationships with clinical characteristics in patients without aura.
Learn More >