Neuralgia

Misexpression and cytosolic retention of peripheral myelin protein 22 (PMP22) within Schwann cells (SCs) is associated with a genetically heterogeneous group of demyelinating peripheral neuropathies. PMP22 overproducer C22 and spontaneous mutant Trembler J (TrJ) mice display neuropathic phenotypes and affected nerves contain abnormally localized PMP22. Nutrient deprivation-induced autophagy is able to suppress the formation of PMP22 aggregates in a toxin-induced cellular model, and improve locomotor performance and myelination in TrJ mice. As a step toward therapies, we assessed whether pharmacological activation of autophagy by rapamycin (RM) could facilitate the processing of PMP22 within neuropathic SCs and enhance their capacity to myelinate peripheral axons. Exposure of mouse SCs to RM induced autophagy in a dose- and time-dependent manner and decreased the accumulation of poly-ubiquitinated substrates. The treatment of myelinating dorsal root ganglion (DRG) explant cultures fr...

We report a case of a 73‐year‐old female who developed unbearable neuropathic pain after a herpes zoster episode. The pain persisted and could not be controlled despite multimodal analgesia. In addition to postherpetic neuralgia, myelitis and complex regional pain syndrome were diagnosed during the evolution of neuropathic pain. This complex neuropathic pain was resolved after sympathetic ganglion block.

The roles of gabapentin and pregabalin are well established in the management of chronic neuropathic pain. Here, we investigated the effectiveness of pregabalin and gabapentin for treating acute neuropathic pain following lumbar discectomy. This prospective, non-randomized, and observational study included 54 patients who experienced acute neuropathic pain after lumbar discectomy. The assessments included the Leeds assessment of neuropathic symptoms and signs scale (LANSS), the Oswestry disability index (ODI), and the visual analog scale (VAS) pre-operatively and at 3 days, 6 months, and 1 year after surgery. The LANSS scores ≧12 suggest the presence of neuropathic pain. Those patients who reported neuropathic pain were randomly treated with gabapentin or pregabalin. In the gabapentin group, the LANSS scores increased to 14 at 3 days after surgery. The patients improved neurologically and on the LANSS, which decreased to 10 points 6 months after surgery and to 4 points at 1 year (P ...

SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. We put rats in a chamber with one half painted white (light area) and the other half painted black (dark area), and measured neuropathic pain-evoked place escape/avoidance paradigm (PEAP) to quantify the level of negative emotion evoked by painful stimuli using a Von Frey hair. Inhibition of CCI-mediated induction of SIP30 by intra-rACC injection of shRNA targeting the rat sip30 gene reduced PEAP. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain such as heat hyperalgesia and mechanical ...

OBJECTIVE Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat–evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber–mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 μV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most...

Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioural side effects were evaluated by assessing beam walking. MIV-247, gabapentin and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 μmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioural deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 μmol/kg) and pregabalin (63-377 μmol/kg) also inhibited mechanical allodynia ...

Herpes zoster (HZ) is a secondary manifestation of a primary infection with varicella-zoster virus (VZV). HZ is caused by reactivation of VZV in the cranial nerves and dorsal spinal root ganglia. VZV, a human herpes virus (HHV3 Human Herpes Virus 3) has a double-stranded linear DNA molecule (Wolff, 1999), has a bilayer lipid shell with surface glycoproteins and an icosahedral capsid. When VZV-specific cellular immunity is impaired, the onset of the disease occurs. A number of therapeutic approaches were available, showing little evidence of effectiveness. However, some therapies seems to be more effective, decreasing the extent and time duration of symptoms and, putatively, the risk of chronic sequelae [e.g. Post-herpetic neuralgia (NPH)]. Ozone has been shown to have an antibacterial and antiviral effect. Antiviral chemotherapy is based on acyclovir, valacyclovir or famcyclovir, with or without prednisolone, but they have little effect on the healing of skin lesions or pain (Wood, ...

Today at the 93rd General Session and Exhibition of the International Association for Dental Research, researcher M.J. Al-Musawi, Newcastle University, Newcastle upon Tyne, UK, will present a study titled "In Vitro Effects of Topical Neuromodulatory Medication on Orofacial Tissue." The IADR General Session is being held in conjunction with the 44th Annual Meeting of the American Association for Dental Research and the 39th Annual Meeting of the Canadian Association for Dental Research.

The mesolimbic reward system plays a critical role in modulating nociception; however, its underlying molecular, cellular, and neural circuitry mechanisms remain unknown. Chronic constrictive injury (CCI) of the sciatic nerve was used to model neuropathic pain. Projection-specific in vitro recordings in mouse brain slices and in vivo recordings from anesthetized animals were used to measure firing of dopaminergic neurons in the ventral tegmental area (VTA). The role of VTA-nucleus accumbens (NAc) circuitry in nociceptive regulation was assessed using optogenetic and pharmacological manipulations, and the underlying molecular mechanisms were investigated by Western blotting, enzyme-linked immunosorbent assays, and conditional knockdown techniques. c-Fos expression in and firing of contralateral VTA-NAc dopaminergic neurons were elevated in CCI mice, and optogenetic inhibition of these neurons reversed CCI-induced thermal hyperalgesia. CCI increased the expression of brain-derived neu...

ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact.MethodsAmbulatory, community‐dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co‐morbidities. Adjusted odds ratios were calculated for follow‐up neuropathy outcomes.ResultsOf 254 participants, 21.3% were women, 57.5% were non‐white. Mean baseline age was 43.5 years. Polyneuropathy prevalence increased from 25.7% to 43.7%. Of 173 participants initially pain‐free, 42 (24.3%) had incident neuropathic pa...

To test if patients with masticatory myofascial pain, local myalgia, centrally mediated myalgia, disc displacement, capsulitis/synovitis, or continuous neuropathic pain differed in self-reported satisfaction with life. The study also tested if satisfaction with life was similarly predicted by measures of physical, emotional, and social functioning across disorders. Satisfaction with life, fatigue, affective distress, social support, and pain data were extracted from the medical records of 343 patients seeking treatment for chronic orofacial pain. Patients were grouped by primary diagnosis assigned following their initial appointment. Satisfaction with life was compared between disorders, with and without pain intensity entered as a covariate. Disorder-specific linear regression models using physical, emotional, and social predictors of satisfaction with life were computed. Patients with centrally mediated myalgia reported significantly lower satisfaction with life than did patients ...

Background: Despite the availability of several drug classes for treatment of neuropathic pain, no one provides the optimal balance of efficacy, tolerability and safety. Paracetamol (acetaminophen) is widely used for reducing pain with various origin around the world. The aim of this study was to compare the analgesic effect of intraperitoneally and intrathecally administration of paracetamol in chronic constriction Injury (CCI) model of the sciatic nerve in male rats. Method: In this study, 24 adult male Wistar rats were randomly divided into 2 groups (n=12). The CCI model of sciatic nerve was used for induction of neuropathic pain. Catheterization was performed on the eleventh day after injury through the space between the L5 and L6. On the fourteen days after injury, paracetamol injected intraperitoneally (100mg/kg) and intrathecally (50μg / rat) in two different groups. Thermal and mechanical hyperalgesia and cold allodynia evaluated 15, 60 and 120 minutes after injection. The i...

Complex regional pain syndrome, formally known as reflex sympathetic dystrophy, is a poorly understood condition that describes a collection of clinical symptoms and signs occurring in the peripheries most commonly after trauma. Pain is the main problem. It is generally out of proportion to the degree of injury and can be unresponsive to narcotics. In addition joint stiffness, temperature and colour changes, and swelling occur. The diagnosis and treatment are challenging for any clinician and a multidisciplinary approach is often necessary with physiotherapy, occupational therapy, and the pain team. The hand surgeon is involved for two reasons, firstly as the upper limb is the most frequently involved, and secondly because the condition may be a complication of the patient’s surgery and result in a much prolonged recovery. This review elucidates the recent advances in the knowledge of the aetiology, classification and treatment of this fascinating condition.

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the Adapter protein-2 Associated Kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase 1 formalin) but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin (STZ) model of diabetic peripheral neuropathy. Usi...

Prikazali smo i razmotrili zanimljivu medicinsku terapiju doktora Giuseppea Moscatija (1880. – 1927.) koji je propisao magnezijev oksid (magnesia usta) pacijentu s dijagnozom “neuralgije celijačnog pleksusa reumatoidnog podrijetla”. Osim tradicionalne upotrebe magnezija kao antacidnog lijeka u to doba, pretpostavili smo da je Moscati propisao magnezij kako bi liječio samu neuralgiju. S obzirom na znanstvenu pozadinu Moscatija u školi Filippa Bottazzija (1867. – 1941.), oca talijanske biokemije, sugerirali smo da je liječnik pokušao primijeniti preliminarne koncepte dobivene iz elektrofizioloških istraživanja na magneziju u svoju kliničku praksu. Tek nakon nekoliko desetljeća magnezij je prepoznat kao temeljni ion u energetskom metabolizmu koji pridonosi održavanju ionske intracelularne homeostaze, uključujući i neurona.

Neurostimulation involves the implantation of devices to stimulate the brain, spinal cord, or peripheral or cranial nerves for the purpose of modulating the neural activity of the targeted structures to achieve specific therapeutic effects. Surgical placement of neurostimulation devices is associated with risks of neurologic injury, as well as possible sequelae from the local or systemic effects of the intervention. The goal of the Neurostimulation Appropriateness Consensus Committee (NACC) is to improve the safety of neurostimulation. The International Neuromodulation Society (INS) is dedicated to improving neurostimulation efficacy and patient safety. Over the past two decades the INS has established a process to use best evidence to improve care. This article updates work published by the NACC in 2014. NACC authors were chosen based on nomination to the INS executive board and were selected based on publications, academic acumen, international impact, and diversity. In areas in w...

The aim of the current study was to estimate the prevalence of all primary headaches and cranial neuralgias in the general community. As part of the population-based Bruneck Study, 574 men and women aged 55–94 years underwent extensive neurological and laboratory examinations involving a standardized headache interview. In the Bruneck Study population the lifetime prevalence of all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%, respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the most common types of headache. In men and women aged 55–94 years the 1-year prevalence of primary headaches was high at 40.5%. In this age range headaches caused significant impairment of health-related quality of life. The Bruneck Study has confirmed the high lifetime prevalence of primary headaches and cranial neuralgias in the general population and provided first valid prevalence data for all primary headaches based on International Classification of H...

The aim of the current study was to estimate the prevalence of all primary headaches and cranial neuralgias in the general community. As part of the population-based Bruneck Study, 574 men and women aged 55–94 years underwent extensive neurological and laboratory examinations involving a standardized headache interview. In the Bruneck Study population the lifetime prevalence of all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%, respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the most common types of headache. In men and women aged 55–94 years the 1-year prevalence of primary headaches was high at 40.5%. In this age range headaches caused significant impairment of health-related quality of life. The Bruneck Study has confirmed the high lifetime prevalence of primary headaches and cranial neuralgias in the general population and provided first valid prevalence data for all primary headaches based on International Classification of H...

Pain may be the most common reason patients seek treatment from physicians. When persistent and unrelieved, pain can frustrate both the person suffering with this condition and the physician trying to alleviate it. Relief from chronic pain may be particularly difficult to achieve and fraught with misconceptions. Treatment usually requires trials of physical, pharmacologic, and surgical interventions to achieve resolution. In cases that remain insoluble, patients must accept partial relief and seek adaptive strategies. The source of persistent pain may be nociceptive or neuropathic. Both utilize the same nervous system pathways for transmission, but significant physiologic differences exist in the mechanism through which the body processes and resolves these painful stimuli. Nociceptive pain that results from a known or obvious source (eg, trauma, cancer metastasis, ischemia, arthritis) is often easy to identify. Neuropathic pain, however, may occur in the absence of an identifiable precipitating cause. Physicians must remain alert to differences in presentation and course of neuropathic pain syndromes, some of which may be subtle or unusual.

In this work, synthetic integration of substituted semicarbazides and various aliphatic, aryl and heteroaryl acids into 1,2,4‐triazol‐5‐ones was accomplished. Following the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluated in two peripheral models of neuropathic pain, the chronic constriction injury and partial sciatic nerve ligation to assess their antihyperalgesic and antiallodynic potential. ED50 studies undertaken for selected compounds exhibiting promising efficacies (1c, 3c and 4a) revealed values ranging from 13.21 to 39.85 mg/kg in four behavioral assays of hyperalgesia and allodynia (spontaneous pain, tactile allodynia, cold allodynia, and mechanical hyperalgesia). Mechanistic studies revealed that the compounds suppressed the inflammatory component of the neuropathic pain inhibiting tumor necrosis factor‐alpha and preventing oxidative and nitrosative stress.