Taylorhickman9985

ter nerve injury are at least partly attributable to blocking propagation of this SA.

Tapering opioids for chronic pain can be challenging for both patients and prescribers, both of whom may be unsure of what to expect in terms of pain, distress, activity interference, and withdrawal symptoms over the first few weeks and months of the taper. To better prepare clinicians to provide patient-centred tapering support, the current research used prospective longitudinal qualitative methods to capture individual-level variation in patients' experience over the first few months of a voluntary physician-guided taper. The research aimed to identify patterns in individuals' experience of tapering and explore whether patient characteristics, readiness to taper, opioid tapering self-efficacy, or psychosocial context were related to tapering trajectory. Twenty-one patients with chronic noncancer pain commencing tapering of long-term opioid therapy were recruited from a metropolitan tertiary pain clinic (n = 13) and a regional primary care practice (n = 8). Semistructured phone interviews were conducted a lient and distressed trajectories, with supportive relationships buffering the effects of adversity for those who followed a resilient trajectory. Discussion focuses on the implications of these findings for the preparation and support of patients with chronic pain who are commencing opioid tapering.

Brain biomarkers of pain, including pain-predictive "signatures" based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. In study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons onal magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. selleck chemicals The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons with painful events were possible. Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.

Different pathophysiological mechanisms contribute to the pain development in osteoarthritis (OA). Sensitization mechanisms play an important role in the amplification and chronification of pain and may predict the therapeutic outcome. Stratification of patients according to their pain mechanisms could help to target pain therapy. This study aimed at developing an easy-to-use, bedside tool-kit to assess sensitization in patients with chronic painful knee OA or chronic pain after total knee replacement (TKR).In total, 100 patients were examined at the most affected knee and extra-segmentally by use of four standardized quantitative sensory testing parameters reflecting sensitization (mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, pressure pain threshold), a bedside testing battery of equivalent parameters including also temporal summation and conditioned pain modulation, and pain questionnaires. Machine learning techniques were applied to identify an appropriate set of itization were pressure pain sensitivity (pain intensity at 4 ml pressure using a 10 ml blunted syringe), mechanical pinprick pain sensitivity (pain intensity of a 0.7 mm nylon-filament) over the most affected knee, and extra-segmental pressure pain sensitivity (pain threshold).This pilot study presents a first attempt to develop an easy-to-use bedside test to probe sensitization in patients with chronic OA knee pain or chronic pain after TKR. This tool may be used to optimize individualized, mechanism-based pain therapy.

Arthropods are the largest group of living organisms, and among them, mosquitoes spread parasites and viruses causing deadly diseases. They can easily spread these pathogens because of their painless skin piercing. Although the lack of pain is mainly due to the thinness of their fascicle, it is possible that mosquito saliva, which is discharged during their piercing, might also contribute to it. If mosquito saliva contains antinociceptive substances, it should act on the sensory neurons innervating the epidermis where there are several ion channels that can detect noxious stimuli, such as the transient receptor potential (TRP) channels. We found that mosquito head homogenates and mouse saliva inhibit TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) channels, either heterologously expressed in HEK293T cells or endogenously expressed in native mouse sensory neurons. Among the different substances contained in mosquito head homogenates or mouse saliva, we have also identified sialorphin as a candidate antinocects of saliva are universal, which could explain why many animals including humans often lick their wounds. These findings would lead to the development of novel and safe antinociceptive agents.

Normalization of the excitatory and inhibitory balance by increasing the levels of endogenous inhibitory neurotransmitters by blocking their reuptake is a promising therapeutic strategy for relieving chronic pain. Pharmacological blockade of spinal GABA transporter subtypes 1 and 3 (GAT1 and GAT3) has been reported to generate analgesic effects in animal models of neuropathic pain. Here we explored the synaptic mechanisms underlying their analgesic effects in the spinal dorsal horn. Whole-cell recordings were made from dorsal horn neurons in spinal slices with attached dorsal roots from adult mice, and the effects of GAT inhibitors on miniature and evoked postsynaptic currents were examined. Behaviorally, GAT inhibitors were intrathecally applied to assess their effects on mechanical hypersensitivity in mice developing neuropathic pain after partial sciatic nerve ligation. The GAT1 inhibitor NNC-711 reduced the frequency of mEPSCs and the amplitude of C-fiber-mediated EPSCs, and the GAT3 inhibitor SNAP-5114ely contributes to their analgesic effects.

Afferents from the C2 spinal nerve (SN) and trigeminal nerve (TN) innervate neighboring cranial territories, and their convergence on the upper cervical dorsal horn neurons represents neural substrate of pain referral in primary headache disorders. Unfortunately, little is known about trigeminocervical input to the major spinal nociceptive projection area lamina I. Here, we used ex vivo brainstem-cervical cord preparation for the visually guided whole-cell recording from the upper cervical lamina I neurons. We show that 50% of them receive convergent monosynaptic input from both nerves, whereas 35% and 11% of neurons receive specific supply from the C2 SN and TN, respectively. Altogether, 10 distinct patterns of synaptic input from the C2 SN and TN to lamina I neurons could be identified. Although stimulation of both nerves evoked excitatory/inhibitory responses, more numerous pure inhibitory inputs arose from the TN. We show that cervical and trigeminal nociceptors converge on to lamina I projection and inther, 10 distinct patterns of synaptic input from the C2 SN and TN to lamina I neurons could be identified. Although stimulation of both nerves evoked excitatory/inhibitory responses, more numerous pure inhibitory inputs arose from the TN. We show that cervical and trigeminal nociceptors converge on to lamina I projection and inhibitory neurons. Thus, trigeminocervical input in lamina I is processed in both nerve-specific and convergent circuitries. Afferent convergence on to inhibitory interneurons serves as a feedforward mechanism balancing excitatory drive to projection neurons. Disruption of this balance may cause pain in primary headache syndromes.

Deprescribing is the systematic process of discontinuing drugs when harms outweigh the benefits. We conducted semistructured telephone interviews with 22 general practitioners (GPs) who had prescribed or deprescribed opioids in patients with chronic noncancer pain within the past 6 months to investigate the barriers and facilitators to deprescribing opioid analgesics in patients with chronic noncancer pain. We also explored GPs' perspectives on the available resources to assist them with opioid deprescribing. Interviews were audio-recorded, transcribed verbatim, and then coded using an iterative process until data saturation reached. The thematic analysis process identified themes, first as concepts, and then refined to overarching themes after the merging of similar subthemes. Themes exploring barriers to deprescribing highlighted the difficulties GPs face while considering patient factors and varying prescribing practices within the confines of the health system. Patient motivation and doctor-patient rappics, they also expressed many barriers relating to managing complex pain conditions, patient factors, and varying prescribing practices between clinicians. Some of these barriers could be mitigated by GPs having time and resources to educate and build rapport with their patients. This suggests the need for further development of multimodal resources and improved support through the public health system to enable GPs to prioritise patient-centred care.

Health care providers, including physical therapists, need to identify the reasons for insufficient physical activity (PA) to assist the 56% to 73% of community-dwelling adults 50 years of age and older who are not performing the recommended 150 minutes of moderate to vigorous PA. Currently, there is no feasible, multifactorial tool to assess PA barriers among this population. Without a tool, health care providers must either rely on self-generated questions or collate results from multiple assessments to identify PA barriers related to personal, social, and environmental factors, which can be time-consuming and incomplete.

To develop the Inventory of Physical Activity Barriers (IPAB), an assessment tool that examines personal, social, and environmental PA barriers.

We developed and psychometrically evaluated the IPAB using a 3-phase process. For phase 1, we used a deductive method to develop the initial scale. During phase 2, we refined the scale and explored its psychometric properties by collecting cross-sectional pilot data on community-dwelling adults 50 years of age and older.