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Pain nerve blockers

Pini Koplovitch, Marshall Devor
Ectopic impulse discharge (ectopia) generated in the soma of afferent neurons in dorsal root ganglia (DRGs) following nerve injury is thought to be a major contributor to neuropathic pain. The DRG is thus a prime interventional target. The process of electrogenesis (impulse generation) in the DRG is far more sensitive to systemically administered Na channel blockers than the process of impulse propagation along sensory axons. It should therefore be possible to selectively suppress DRG ectopia with local application of membrane stabilizing agents without blocking normal impulse traffic...
March 12, 2018: Pain
Tânia C Gonçalves, Rachid Boukaiba, Jordi Molgó, Muriel Amar, Michel Partiseti, Denis Servent, Evelyne Benoit
The Chinese bird spider huwentoxin-IV (HwTx-IV) is well-known to be a highly potent blocker of NaV 1.7 subtype of voltage-gated sodium (NaV ) channels, a genetically validated analgesic target, and thus promising as a potential lead molecule for the development of novel pain therapeutics. In the present study, the interaction between HwTx-IV and NaV 1.6 channel subtype was investigated using multiscale (from in vivo to individual cell) functional approaches. HwTx-IV was approximatively 2 times more efficient than tetrodotoxin (TTX) to inhibit the compound muscle action potential recorded from the mouse skeletal neuromuscular system in vivo, and 30 times more effective to inhibit nerve-evoked than directly-elicited muscle contractile force of isolated mouse hemidiaphragms...
February 20, 2018: Neuropharmacology
Wen Chen, Ye-Nan Chi, Xue-Jing Kang, Qing-Ying Liu, Hao-Lin Zhang, Zhi-Hua Li, Zi-Fang Zhao, Yin Yang, Li Su, Jie Cai, Fei-Fei Liao, Ming Yi, You Wan, Feng-Yu Liu
Injuries to peripheral nerve fibers induce neuropathic pain. But the involvement of adjacent uninjured fibers to pain is not fully understood. The present study aims to investigate the possible contribution of Cav 3.2 T-type calcium channels in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve injury (SNI). Aβ-, Aδ- and C-fibers of the uninjured sural nerve were sensitized revealed by in vivo single-unit recording, which were accompanied by accumulation of Cav 3.2 T-type calcium channel proteins shown by Western blotting...
2018: Frontiers in Molecular Neuroscience
Xiaonan Liang, Gang Yu, Ruibin Su
Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II trials), but it failed to ameliorate neuropathic low back pain in Phase III trials. It is unclear whether ralfinamide is effective against neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of ralfinamide in neuropathic pain models induced by spared nerve injury and chemotherapy were compared in a gabapentin-controlled manner...
January 30, 2018: European Journal of Pharmacology
Zhiyu Chen, Xiaolu Shen, La Huang, Hai Wu, Mazhong Zhang
The pathophysiology of neuropathic pain generation has not been fully investigated. Previous studies have primarily focused on changes in the properties of single neurons in the brain after nerve injury; however, little is known concerning the role of neuron-to-neuron connections in neuropathic pain pathogenesis. Synaptic transmission potentiation in anterior cingulate cortex (ACC) has been confirmed to be responsible for the formation of neuropathic pain. Thus, analysis of interneuronal connections in the ACC is an important approach for understanding the mechanism of neuropathic pain since it provides information on the potency of synaptic transmission...
January 26, 2018: Scientific Reports
Weihua Ding, Zerong You, Shiqian Shen, Jinsheng Yang, Grewo Lim, Jason T Doheny, Shengmei Zhu, Yi Zhang, Lucy Chen, Jianren Mao
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. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with trigeminal nerve injury...
January 31, 2018: Journal of Pain: Official Journal of the American Pain Society
Abdulaziz Adel Almobarak, Abdullah AlShammari, Reham I Alhomoudi, Abdulaziz M Eshaq, Sara Mujahid Algain, Elyse C Jensen, Shamayel Mohammed, Khaled Al-Kattan, Zeina Kayali, Abdulhadi A AlAmodi
BACKGROUND Primary pericardial tumors have a prevalence of between 6.7% and 12.8% of all tumors arising in the cardiac region. Pericardial schwannoma is a rare entity. It arises from the cardiac plexus and vagus nerve innervating the heart. Most of the reported cases, have presented with benign behavior, however, in rare situations, they can undergo transformation to malignant behavior When comparing the prevalence of cardiac tumors to that of pericardial tumors, the latter is much lower in occurrence. A review of English literature identified six pericardial schwannoma cases...
January 24, 2018: American Journal of Case Reports
B Sagalajev, H Wei, Z Chen, I Albayrak, A Koivisto, A Pertovaara
Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI)...
December 20, 2017: Neuroscience
Dulguun Batbold, Masamichi Shinoda, Kuniya Honda, Akihiko Furukawa, Momoko Koizumi, Ryuta Akasaka, Satoshi Yamaguchi, Koichi Iwata
BACKGROUND: Accidental mandibular nerve injury may occur during tooth extraction or implant procedures, causing ectopic orofacial pain. The exact mechanisms underlying ectopic orofacial pain following mandibular nerve injury is still unknown. Here, we investigated the role of macrophages and tumor necrosis factor alpha (TNFα) in the trigeminal ganglion (TG) in ectopic orofacial pain following inferior alveolar nerve transection (IANX). METHODS: IANX was performed and the mechanical head-withdrawal threshold (MHWT) in the whisker pad skin ipsilateral to IANX was measured for 15 days...
December 16, 2017: Journal of Neuroinflammation
Kaede Kakita, Hirona Tsubouchi, Mayu Adachi, Shiori Takehana, Yoshihito Shimazu, Mamoru Takeda
Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats...
November 29, 2017: Neuroscience Research
Takayoshi Masuoka, Juana Gallar, Carlos Belmonte
PURPOSE: Chronic dryness of the ocular surface evokes sensitization of corneal cold-sensitive neurons through an increase of sodium currents and a decrease of potassium currents, leading to the unpleasant dryness and pain sensations typical of dry eye disease. Here, we explored the effects of amitriptyline, a voltage-gated Na+ channel blocker used for the treatment of depression and chronic pain, on nerve terminal impulse (NTI) activity of cold-sensitive nerve terminals recorded in intact and tear-deficient guinea pig corneas...
January 2018: Journal of Ocular Pharmacology and Therapeutics
Gricel Riquelme, Joaquín M Sepúlveda, Zaki Al Ghumgham, Miguel Del Campo, Cecilia Montero, Nestor Lagos
Local anesthesia is an effective method to control pain. Neosaxitoxin is a phycotoxin whose molecular mechanism includes a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. The present study was designed to evaluate the clinical efficacy of Neosaxitoxin as a local long-acting pain blocker in horse bucked shins, and it was found to effectively control pain. While Neosaxitoxin and Gonyautoxin, another Paralytic Shellfish Poison (PSP) toxin, have been successfully used in humans as long-lasting pain blockers, this finding marks the first time a PSP has been shown to have an established effect in veterinary medicine...
January 2018: Toxicon: Official Journal of the International Society on Toxinology
Shiao-Jin Guu, Jiun-Hung Geng, I-Ting Chao, Hui-Tzu Lin, Yung-Chin Lee, Yung-Shun Juan, Chia-Chu Liu, Chii-Jye Wang, Chia-Chun Tsai
Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy...
October 1, 2017: American Journal of Men's Health
Prashant S Korat, Pankaj P Kapupara
The body areas from where sutures are removed later, where wound healing is delayed. Epidural analgesia is the most effective method but could not be used for postoperative pain. Peripheral nerve blockers also provided excellent analgesia but are not effective in postoperative pain. Infiltration of the surgical wound with local anesthetics is decreased postoperative pain by inhibiting transmission of noxious impulses at the site. The objective of the study was to explore the effect of the local infiltration of the surgical wounds with low-dose of levobupivacaine, ibuprofen, and epinephrine over the sutured muscle wound in postoperative pain...
September 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mohammad Zakir Hossain, Shumpei Unno, Hiroshi Ando, Yuji Masuda, Junichi Kitagawa
Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia...
September 26, 2017: International Journal of Molecular Sciences
Torsten Kraya, Stephan Mages, Stephan Zierz
Background and objectives Abdominal pain is a well-known headache-associated symptom in migraine in children, but rarely in adults. We describe a case of a female patient with typical accompanying migraine symptoms without headache but with thoracic pain. Case report The present case of a 41 year-old-woman shows recurrent attacks with thoracic pain and typical accompanying migraine symptoms but without headache. Symptoms resolved upon treatment with triptans and beta blockers. Discussion This case might be interpreted as "thoracic migraine", and extends the spectrum of migraine forms...
January 1, 2017: Cephalalgia: An International Journal of Headache
Flavien Bessaguet, Aurore Danigo, Laurent Magy, Franck Sturtz, Alexis Desmoulière, Claire Demiot
Sensory defects associated with small-fiber neuropathy (SFN) can lead to profound disabilities. The relationship between the sensory nervous system and modulation of the renin-angiotensin system (RAS) has been described and focused on pain and neurodegeneration in several animal models. We have recently developed an experimental model of functional sensory neuropathy showing thermal hypoalgesia and neuropeptide depletion without nerve fiber degeneration. Here, we aimed to determine whether the modulation of angiotensin II (Ang II) activity could prevent sensory neuropathy induced by RTX...
September 5, 2017: Neuropharmacology
Walter Hermann, Sevdalina Lambova, Ulf Müller-Ladner
Background: Osteoarthritis (ОА) is the most common joint disease and a leading cause for impaired function and disability with significant treatment costs and socio-economic burden. Despite recent achievements in the knowledge on disease pathogenesis, the treatment is still a challenge and contrary to inflammatory joint diseases, no disease-modifying drugs are currently available for OA. Objectives: Despite recent achievements in the knowledge on disease pathogenesis, the treatment is still a challenge and contrary to inflammatory joint diseases, no disease-modifying drugs are currently available for OA...
August 29, 2017: Current Rheumatology Reviews
Lou Mikuzuki, Hiroto Saito, Ayano Katagiri, Shinji Okada, Shiori Sugawara, Asako Kubo, Kinuyo Ohara, Jun Lee, Akira Toyofuku, Koichi Iwata
Iatrogenic trigeminal nerve injuries remain a common and complex clinical problem. Satellite glial cell (SGC) activation, associated phosphorylation of extracellular signal-regulated kinase (ERK), and neuropeptide expression in the trigeminal ganglion (TG) are known to be involved in trigeminal neuropathic pain related to trigeminal nerve injury. However, the involvement of these molecules in orofacial neuropathic pain mechanisms is still unknown. Phosphorylation of ERK1/2 in lingual nerve crush (LNC) rats was observed in SGCs...
August 23, 2017: European Journal of Neuroscience
Shigeaki Kawai, Tokuhiro Yamada, Tadashi Matsuura, Tomoharu Funao, Kiyonobu Nishikawa
AIMS: The relationship between neuropathic pain and myocardial infarction (MI) was uncertain because of some medication or underlying diseases. This study investigated the impact of neuropathic pain on ischemia reperfusion injury using isolated rat hearts and cardiomyocytes. MAIN METHODS: Male Sprague-Dawley rats were assigned to the control and allodynia (AL) groups, with the latter subjected to the fifth lumbar spinal-nerve ligation. First, isolated hearts underwent 25-min ischemia and 90-min reperfusion to assess hemodynamic changes and MI area...
October 15, 2017: Life Sciences
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