Electrophysiological characterisation of central sensitisation in canine spontaneous osteoarthritis.

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.

Cognitive impairment in a rat model of neuropathic pain: role of hippocampal microtubule stability.

Clinical evidence indicates that cognitive impairment is a common comorbid condition of chronic pain. However, the cellular basis for chronic pain-mediated cognitive impairment remains unclear. We report here that rats exhibited memory deficits after spared nerve injury (SNI).

Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs.

Background: Sucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress-related mucosal diseases (SRMD) in dogs is unknown.

Hypothesis/objectives: To develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model.

Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain.

Unlabelled: Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are involved in the development and maintenance of chronic pain. However, the effect of HCN channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not been examined.

Different effects of dexmedetomidine and midazolam on the expression of NR2B and GABAA-α1 following peripheral nerve injury in rats.

Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model.

Spontaneous painful disease in companion animals can facilitate the development of chronic pain therapies for humans.

Objective: To outline the role that spontaneous osteoarthritis (OA) in companion animals can play in translational research and therapeutic pharmacological development.

Outline: Narrative review summarizing the opportunities and limitations of naturally occurring, spontaneous OA as models of human OA pain, with a focus on companion animal pets. The background leading to considering inserting spontaneous disease models in the translational paradigm is provided.

Ultrasmall Superparamagnetic Iron Oxide Imaging Identifies Tissue and Nerve Inflammation in Pain Conditions.

Objective: Correlation between radiologic structural abnormalities and clinical symptoms in low back pain patients is poor. There is an unmet clinical need to image inflammation in pain conditions to aid diagnosis and guide treatment. Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is clinically used to treat iron deficiency anemia and showed promise in imaging tissue inflammation in human.

Chronic maladaptive pain in cats: A review of current and future drug treatment options.

Despite our increasing understanding of the pathophysiology underlying chronic or maladaptive pain, there is a significant gap in our ability to diagnose and treat the condition in domestic cats. Newer techniques being used to identify abnormalities in pain processing in the cat include validated owner questionnaires, measurement of movement and activity, and measurement of sensory thresholds and somatomotor responses. While some data are available evaluating possible therapeutics for the treatment of chronic pain in the cat, most data are limited to normal cats.

Gut microbiota is critical for the induction of chemotherapy-induced pain.

Chemotherapy-induced pain is a dose-limiting condition that affects 30% of patients undergoing chemotherapy. We found that gut microbiota promotes the development of chemotherapy-induced mechanical hyperalgesia. Oxaliplatin-induced mechanical hyperalgesia was reduced in germ-free mice and in mice pretreated with antibiotics.

Nortriptyline Enhances Morphine-Conditioned Place Preference in Neuropathic Rats: Role of the Central Noradrenergic System.

Background: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats.

Management of chronic pain using complementary and integrative medicine.

Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic pain is the leading indication for use of CIM, and about 33% of adults and 12% of children in the US have used it in this context. Although advances have been made in treatments for chronic pain, it remains inadequately controlled for many people.

Adult spinal cord neurogenesis: A regulator of nociception.

Adult spinal cord neurogenesis occurs at low, constant rate under normal conditions and can be amplified by pathologic conditions such as injury or disease. The immature neurons produced through adult neurogenesis have increased excitability and migrate preferentially to the superficial dorsal horn layers responsible for nociceptive signaling. Under normal conditions, this process may be responsible for maintaining a steady-state, but adaptable level of nociceptive sensitivity, thus representing an experience-dependent mechanism of regulation similar to other neurogenic niches.

Thermal QST Phenotypes Associated with Response to Lumbar Epidural Steroid Injections: A Pilot Study.

Objective: Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI).

Design: Prospective, observational pilot study.

An Improved Rodent Model of Trigeminal Neuropathic Pain by Unilateral Chronic Constriction Injury of Distal Infraorbital Nerve.

Unlabelled: The number of studies on trigeminal nerve injury using animal models remains limited. A rodent model of trigeminal neuropathic pain was first developed in 1994, in which chronic constriction injury (CCI) is induced by ligation of the infraorbital nerve (IoN). This animal model has served as a major tool to study trigeminal neuropathic pain.

Defining local nerve blocks for feline distal pelvic limb surgery: a cadaveric study.

Objectives Anatomical and methodological detail is lacking regarding local anesthetic peripheral nerve block techniques for distal pelvic limb surgery in cats. The aim of this study was to develop, describe and test nerve block methods based on cadaveric dissections and dye injections. Methods Ten pairs of feline pelvic limbs (n = 20) were dissected and the tibial nerve (T n.

Peripheral nerve injury induces adult brain neurogenesis and remodelling.

Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons.

Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined.

Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis.

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model.

Neuropeptide S modulates the amygdaloidal HCN activities (Ih) in rats: Implication in chronic pain.

Neuropeptide S (NPS), an endogenous anxiolytic, has been shown to protect against chronic pain through interacting with its cognate NPS receptor (NPSR) in the brain. However, the cellular mechanism of this NPS action remains unclear. We report that NPS inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel current (Ih) in the rat's amygdala through activation of NPSR.

A Correlative Relationship Between Chronic Pain and Insulin Resistance in Zucker Fatty Rats: Role of Downregulation of Insulin Receptors.

Unlabelled: Epidemiological studies and meta-analyses report a strong relationship between chronic pain and abnormalities in glucose metabolism, but the exact relationship between chronic pain and insulin resistance in type 2 diabetes (T2D) remains unknown. Using a model of neuropathic thermal and tactile hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in Zucker Diabetic Fatty (ZDF) and Zucker Lean (ZL) littermates, we compared the recovery period of hypersensitivity and the progression of T2D and studied the possible involvement of insulin receptors (IRs) in the comorbidity of these 2 conditions. We found that the nociceptive thresholds to thermal and mechanical stimulation in naive ZDF rats were lower than in ZL littermates at 6 weeks of age.

Profiles of Urine Drug Test in Clinical Pain Patients vs Pain Research Study Subjects.

Objective: To examine similarities and differences in urine drug test (UDT) results in clinical pain patients and pain subjects participating in pain research studies.

Design: An observational study with retrospective chart review and data analysis.

Methods: We analyzed 1,874 UDT results obtained from 1) clinical pain patients (Clinical Group; n = 1,529) and 2) pain subjects consented to participate in pain research studies (Research Group; n = 345).

Immature spinal cord neurons are dynamic regulators of adult nociceptive sensitivity.

Chronic pain is a debilitating condition with unknown mechanism. Nociceptive sensitivity may be regulated by genetic factors, some of which have been separately linked to neuronal progenitor cells and neuronal differentiation. This suggests that genetic factors that interfere with neuronal differentiation may contribute to a chronic increase in nociceptive sensitivity, by extending the immature, hyperexcitable stage of spinal cord neurons.

Effects of Spinal Cord Stimulation on Pain Thresholds and Sensory Perceptions in Chronic Pain Patients.

Objective: Spinal cord stimulation (SCS) has been in clinical use for nearly four decades. In earliest observations, researchers found a significant increase in pain threshold during SCS therapy without changes associated with touch, position, and vibration sensation. Subsequent studies yielded diverse results regarding how SCS impacts pain and other sensory thresholds.