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https://www.readbyqxmd.com/read/29679483/prostaglandin-fp-receptor-antagonists-discovery-pharmacological-characterization-and-therapeutic-utility
#1
REVIEW
Najam A Sharif, Peter G Klimko
In contrast to the availability of potent and selective antagonists of several prostaglandin (PG) receptor types (including DP1 , DP2 , EP, and TP receptors), there has been a paucity of well-characterized, selective FP-receptor antagonists. The earliest ones included dimethyl amide and dimethyl amine derivatives of PGF2α , but these have failed to gain prominence. The fluorinated PGF2α analogs, AL-8810 and AL-3138, were subsequently discovered as competitive and non-competitive FP-receptor antagonists, respectively...
April 21, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29678597/anxiety-but-not-depressive-like-behaviors-are-related-to-facial-hyperalgesia-in-a-model-of-trigeminal-neuropathic-pain-in-rats
#2
Eder Gambeta, Marcio Augusto Batista, Gabriel Paz Maschio, Joelle de Melo Turnes, Erika Ivanna Araya, Juliana Geremias Chichorro
Trigeminal neuralgia (TN) is a painful condition characterized by excruciating facial pain, which has a serious impact on quality of life. Depression and anxiety have been commonly associated with TN, but clinical studies report that these comorbidities are frequently underdiagnosed and undertreated in TN patients. Herein it was investigated if rats submitted to the infraorbital nerve constriction (CION), a model of trigeminal neuropathic pain, would display anxiety- and depressive-like behaviors in addition to the facial sensory changes in different time points after the nerve injury...
April 17, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29673859/orofacial-neuropathic-pain-reduces-spontaneous-burrowing-behavior-in-rats
#3
K Deseure, G Hans
It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow...
April 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29672450/downregulation-of-adenosine-and-adenosine-1-receptor-contributes-to-neuropathic-pain-in-resiniferatoxin-neuropathy
#4
Hung-Wei Kan, Chin-Hong Chang, Chih-Lung Lin, Yi-Chen Lee, Sung-Tsang Hsieh, Yu-Lin Hsieh
The neurochemical effects of adenosine signaling in small-fiber neuropathy leading to neuropathic pain are yet to be explored in a direct manner. This study examined this system at the level of ligand (via the ectonucleotidase activity of prostatic acid phosphatase, PAP) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder which specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion neurons (DRG), high-performance liquid chromatography (HPLC) for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy...
April 16, 2018: Pain
https://www.readbyqxmd.com/read/29672449/cortical-astrocytes-prime-the-induction-of-spine-plasticity-and-mirror-image-pain
#5
Tatsuya Ishikawa, Kei Eto, Sun Kwang Kim, Hiroaki Wake, Ikuko Takeda, Hiroshi Horiuchi, Andrew J Moorhouse, Hitoshi Ishibashi, Junichi Nabekura
Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Since synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo two-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 following a peripheral nerve injury...
April 16, 2018: Pain
https://www.readbyqxmd.com/read/29671236/picroside-ii-attenuates-cci-induced-neuropathic-pain-in-rats-by-inhibiting-spinal-reactive-astrocyte-mediated-neuroinflammation-through-the-nf-%C3%AE%C2%BAb-pathway
#6
Xiaolian Nong, Yuyan Lan
Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)...
April 18, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29670396/sustained-analgesic-effect-of-clonidine-co-polymer-depot-in-a-porcine-incisional-pain-model
#7
Jared T Wilsey, Julie H Block
Background: Previous research suggests that the α2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action. Purpose: The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29659469/alloknesis-and-hyperknesis-mechanisms-assessment-methodology-and-clinical-implications-of-itch-sensitization
#8
Hjalte Holm Andersen, Tasuku Akiyama, Leigh Ann Nattkemper, Antoinette van Laarhoven, Jesper Elberling, Gil Yosipovitch, Lars Arendt-Nielsen
Itch and pain share numerous mechanistic similarities. Patients with chronic itch conditions (for instance atopic dermatitis or neuropathic itch), often experience symptoms such as mechanical alloknesis and hyperknesis. These dysesthesias are analoguous to the pain-associated phenomena allodynia and hyperalgesia, which are often observed, e.g., in neuropathic pain conditions. Mechanical itch dysesthesias represent abnormal sensory states (caused by neuroplastic changes) wherein considerable itch is evoked, for instance by light cutaneous stimuli such as from clothing (alloknesis), or where increased itch is perceived in response to normally itch-evoking stimuli (hyperknesis)...
April 11, 2018: Pain
https://www.readbyqxmd.com/read/29653184/estrogen-alleviates-neuropathic-pain-induced-after-spinal-cord-injury-by-inhibiting-microglia-and-astrocyte-activation
#9
Jee Youn Lee, Hae Young Choi, Bong Gun Ju, Tae Young Yune
Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17β-estradiol (100, 300 μg/kg) were administered to rats with neuropathic pain after SCI through intravenous injection...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29652665/effect-of-flavonol-and-its-dimethoxy-derivatives-on-paclitaxel-induced-peripheral-neuropathy-in-mice
#10
Vijaykumar Sayeli, Jagan Nadipelly, Parimala Kadhirvelu, Binoy Varghese Cheriyan, Jaikumar Shanmugasundaram, Viswanathan Subramanian
BACKGROUND: Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3',4'-dimethoxy flavonol, 6,3'-dimethoxy flavonol, 7,2'-dimethoxy flavonol and 7,3'-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice. METHODS: A single dose of paclitaxel (10 mg/kg, i...
April 13, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29650413/taurine-protects-against-knee-osteoarthritis-development-in-experimental-rat-models
#11
Yiqun Bian, Meng Zhang, Kai Wang
BACKGROUND: Osteoarthritis (OA) is one of the complex diseases that affect a large population of the world. The aim of the current study was to explore the roles of taurine in OA rat models, and discover the related mechanisms. METHODS: OA rat models were established by anterior cruciate ligament transection (ACLT) plus medial meniscus resection (MMx) surgery on the right knees. Secondary mechanical allodynia, weight-bearing alterations and knee joint width were evaluated before surgery and every two weeks after surgery...
April 9, 2018: Knee
https://www.readbyqxmd.com/read/29642930/neuropeptide-regulation-of-adaptive-immunity-in-the-tibia-fracture-model-of-complex-regional-pain-syndrome
#12
Wen-Wu Li, Tian-Zhi Guo, Xiaoyou Shi, Frank Birklein, Tanja Schlereth, Wade S Kingery, J David Clark
BACKGROUND: Both dysfunctional neuropeptide signaling and immune system activation are characteristic of complex regional pain syndrome (CRPS). Unknown is whether substance P (SP) or calcitonin gene-related peptide (CGRP) support autoantibody production and, consequently, nociceptive sensitization. METHODS: These experiments involved the use of a well-characterized tibia fracture model of CRPS. Mice deficient in SP expression (Tac1-/- ) and CGRP signaling (RAMP1-/- ) were used to probe the neuropeptide dependence of post-fracture sensitization and antibody production...
April 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29628771/activation-of-spinal-dorsal-horn-p2y-13-receptors-can-promote-the-expression-of-il-1%C3%AE-and-il-6-in-rats-with-diabetic-neuropathic-pain
#13
Rui Zhou, Tao Xu, XiaoHong Liu, YuanShou Chen, DeYing Kong, Hong Tian, Mingxia Yue, Dujuan Huang, Junwei Zeng
Objective: The dorsal horn P2Y13 receptor is involved in the development of pain behavior induced by peripheral nerve injury. It is unclear whether the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 at the spinal dorsal horn are influenced after the activation of P2Y13 receptor in rats with diabetic neuropathic pain (DNP). Methods: A rat model of type 1 DNP was induced by intraperitoneal injection of streptozotocin (STZ). We examined the expression of P2Y13 receptor, Iba-1, IL-1β, IL-6, JAK2, STAT3, pTyr1336 , and pTyr1472 NR2B in rat spinal dorsal horn...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29625610/a-novel-interaction-between-cx-3-cr-1-and-ccr-2-signalling-in-monocytes-constitutes-an-underlying-mechanism-for-persistent-vincristine-induced-pain
#14
Karli Montague, Raffaele Simeoli, Joao Valente, Marzia Malcangio
BACKGROUND: A dose-limiting side effect of chemotherapeutic agents such as vincristine (VCR) is neuropathic pain, which is poorly managed at present. Chemokine-mediated immune cell/neuron communication in preclinical VCR-induced pain forms an intriguing basis for the development of analgesics. In a murine VCR model, CX3 CR1 receptor-mediated signalling in monocytes/macrophages in the sciatic nerve orchestrates the development of mechanical hypersensitivity (allodynia). CX3 CR1 -deficient mice however still develop allodynia, albeit delayed; thus, additional underlying mechanisms emerge as VCR accumulates...
April 6, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29623757/icariin-a-flavonoid-with-anti-cancer-effects-alleviated-paclitaxel-induced-neuropathic-pain-in-a-sirt1-dependent-manner
#15
Yulong Gui, Jie Zhang, Liang Chen, Shunyuan Duan, Jing Tang, Wei Xu, Aiyuan Li
Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29619928/studies-of-upper-limb-pain-in-occupational-medicine-in-general-practice-and-among-computer-operators
#16
Jørgen Riis Jepsen
Diagnostic consensus criteria cannot be applied in a major proportion of patients with upper limb complaints, many of which are regarded as "non-specific". The three empirical studies in this thesis aimed to address this diagnostic challenge by incorporating representative neurological qualities in the physical examination.
Patterns of muscle weakness, sensory abnormalities and nerve trunk allodynia based on the nerves' topography and their motor and cutaneous innervation were defined to reflect peripheral nerve afflictions and their locations...
April 2018: Danish Medical Journal
https://www.readbyqxmd.com/read/29619074/involvement-of-mrgprc-in-electroacupuncture-analgesia-for-attenuating-cfa-induced-thermal-hyperalgesia-by-suppressing-the-trpv1-pathway
#17
Ying-Jun Liu, Xiao-Xi Lin, Jian-Qiao Fang, Fang Fang
Mas-related G-protein-coupled receptor C (MrgprC) plays an important role in modulating chronic inflammatory pain. Electroacupuncture (EA) has a satisfactory analgesic effect on chronic pain. This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain. Chronic inflammatory pain was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the left hind paw. EA (2/100 Hz) stimulation was administered...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29616392/pain-relieving-effectiveness-of-co-treatment-with-local-tramadol-and-systemic-minocycline-in-carrageenan-induced-inflammatory-pain-model
#18
Tufan Mert, Emel Sahin, Selma Yaman, Mehmet Sahin
In this study, we tested our working hypothesis that inhibiting the activation of microglia by systemic minocycline treatments can decrease the dosage of local tramadol injection in inflammatory pain. This study was therefore aimed to evaluate the actions of intraplantarly injected tramadol, intraperitoneally injected minocycline, or their combined treatments on the inflammation-induced hypernociception (thermal hyperalgesia, mechanical allodynia), edema, and pro- and anti-inflammatory cytokine levels of paw and spinal cord tissues in a rat model of carrageenan-induced hindpaw inflammation...
April 3, 2018: Inflammation
https://www.readbyqxmd.com/read/29615898/antihyperalgesic-properties-of-honokiol-in-inflammatory-pain-models-by-targeting-of-nf-%C3%AE%C2%BAb-and-nrf2-signaling
#19
Sidra Khalid, Muhammad Z Ullah, Ashraf U Khan, Ruqayya Afridi, Hina Rasheed, Adnan Khan, Hussain Ali, Yeong S Kim, Salman Khan
The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis , in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29614007/pepsin-egg-white-hydrolysate-improves-glucose-metabolism-complications-related-to-metabolic-syndrome-in-zucker-fatty-rats
#20
Marta Garcés-Rimón, Cristina González, Gema Vera, José-A Uranga, Rosina López-Fandiño, Visitación López-Miranda, Marta Miguel
The purpose of this study was to evaluate the effect of the administration of two egg white hydrolysates on glucose metabolism complications related to Metabolic Syndrome (MS) in Zucker fatty rats (ZFR). ZFR were given 750 mg/kg/day of egg white hydrolyzed with pepsin (HEW1) or with aminopeptidase (HEW2) for 12 weeks in their drinking water or just water. Zucker lean rats (ZLR), which received water, were used as a control. The presence of tactile allodynia, which is a sign of peripheral neuropathy, was assessed...
April 3, 2018: Nutrients
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