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Neuropathic Pain OR Refractory Pain

Fei Dou, Xudong Cao, Peng Jing, Chunyan Wu, Yuxin Zhang, Yin Chen, Guisen Zhang
The synthesis and H3 receptor ligand of a new series of lactam derivatives are reported. The new compounds were evaluated in vitro in H3 and H1 receptor-binding assays. The structure-activity relationship led us to the promising derivative 2-methyl-7-(3-morpholinopropoxy)-3,4-dihydroisoquinolin-1(2H)-one (11). The compound with highest affinity and greatest selectivity were further profiled, In addition, compound 11 exerted dose-dependent anti-nociceptive effects in the formalin test. These characteristics suggested that the potent and selective compound 11 could be a potent candidate for pain treatment...
April 8, 2019: Bioorganic & Medicinal Chemistry Letters
Xiao-Fang Mao, Hai-Yun Wu, Xue-Qi Tang, Usman Ali, Hao Liu, Yong-Xiang Wang
BACKGROUND: The G protein-coupled receptor 40 (GPR40), broadly expressed in various tissues such as the spinal cord, exerts multiple physiological functions including pain regulation. This study aimed to elucidate the mechanisms underlying GPR40 activation-induced antinociception in neuropathic pain, particularly related to the spinal glial expression of IL-10 and subsequent β-endorphin. METHODS: Spinal nerve ligation-induced neuropathic pain model was used in this study...
April 13, 2019: Journal of Neuroinflammation
Wolfgang Jaksch, Rudolf Likar, Martin Aigner
Although ketamine has been known and clinically applied for a long time, questions still arise around the many possible indications in which the anesthetic and analgesic substance could be used. In particular, these questions relate to new indications in which ketamine is used in low subanesthetic doses.The mechanism of action at the NMDA receptor clearly distinguishes ketamine from all other analgesics. Possible applications include the prevention of chronic postoperative pain as well as the treatment of neuropathic pain...
April 12, 2019: Wiener Medizinische Wochenschrift
Ayah Shakshuki, Pollen Yeung, Remigius U Agu
OBJECTIVES: To investigate the stability and beyond-use date (BUD) of topical gabapentin in 3 commonly used bases. METHODS: Lipoderm cream, Versabase gel, and Emollient cream were used to compound gabapentin (10%). The products were stored in Ecolojars, kept at 25°C, 4°C, and 40°C, and samples were collected on different days (days 0, 14, 28, and 90). Potency, stability, and organoleptic changes were monitored. RESULTS: At 25°C and 40°C, the potency of gabapentin in Lipoderm cream significantly increased (P < 0...
April 9, 2019: Journal of the American Pharmacists Association: JAPhA
Miguel M Garcia, Carlos Goicoechea, Martín Avellanal, Susana Traseira, Ma Isabel Martín, Eva Ma Sánchez-Robles
Oxycodone and morphine are two opioid drugs commonly used for the treatment of moderate to severe pain. However, their use in the management of noncancer pain remains a controversial issue and, in this respect, the evidence on their effectiveness and safety, particularly in osteoarthritis, is being questioned. In order to analyse their analgesic profile, two different pain models in rats were used: the formalin-induced inflammatory pain and the monosodium iodoacetate (MIA)-induced knee osteoarthritic pain. Drugs were administered systemically (i...
April 9, 2019: European Journal of Pharmacology
Liuyue Yang, Weihua Ding, Zerong You, Jinsheng Yang, Shiqian Shen, Jason T Doheny, Lucy Chen, Ruhui Li, Jianren Mao
INTRODUCTION: The aim of this study was to examine the effect of electroacupuncture (EA) on trigeminal neuropathic pain in rats and explore the potential mechanism underlying the putative therapeutic effect of EA. METHODS: Trigeminal neuropathic pain behavior was induced in rats by unilateral chronic constriction injury of the distal infraorbital nerve (dIoN-CCI). EA was administered at ST2 ( Sibai) and Jiachengjiang. A total of 60 Sprague Dawley rats were divided into the following four groups ( n = 15 per group) to examine the behavioral outcomes after surgery and/or EA treatment: sham (no ligation); dIoN-CCI (received isoflurane only, without EA treatment); dIoN-CCI+EA-7d (received EA treatment for 7 days); and dIoN-CCI+EA-14d (received EA treatment for 14 days)...
April 12, 2019: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
Caijuan Li, Yanying Lei, Yi Tian, Shiqin Xu, Xiaofeng Shen, Haibo Wu, Senzhu Bao, Fuzhou Wang
No abstract text is available yet for this article.
April 12, 2019: Molecular Pain
Li-Na Huang, Yun Zou, Shao-Gen Wu, Hong-Hong Zhang, Qing-Xiang Mao, Jin-Bao Li, Yuan-Xiang Tao
Fibroblast growth factor-inducible-14 (Fn14), a receptor for tumor necrosis-like weak inducer of apoptosis, is expressed in the neurons of dorsal root ganglion (DRG). Its mRNA is increased in the injured DRG following peripheral nerve injury. Whether this increase contributes to neuropathic pain is unknown. We reported here that peripheral nerve injury caused by spinal nerve ligation (SNL) increased the expression of Fn14 at both protein and mRNA levels in the injured DRG. Blocking this increase attenuated the development of SNL-induced mechanical, thermal, and cold pain hypersensitivities...
April 11, 2019: Molecular Neurobiology
Bryn C Taylor, Christopher T Lee, Rommie E Amaro
CC chemokine receptor 2 (CCR2) is a part of the chemokine receptor family, an important class of therapeutic targets. These class A G-protein coupled receptors (GPCRs) are involved in mammalian signaling pathways and control cell migration toward endogenous CC chemokine ligands, named for the adjacent cysteine motif on their N terminus. Chemokine receptors and their associated ligands are involved in a wide range of diseases and thus have become important drug targets. CCR2, in particular, promotes the metastasis of cancer cells and is also implicated in autoimmunity-driven type-1 diabetes, diabetic nephropathy, multiple sclerosis, asthma, atherosclerosis, neuropathic pain, and rheumatoid arthritis...
April 11, 2019: Proceedings of the National Academy of Sciences of the United States of America
Agnieszka Gunia-Krzyżak, Florence M Bareyre, Henryk Marona, Anna M Waszkielewicz
Epilepsy and neuropathic pain are frequent neurological disorders with pathomechanism based on abnormal neuronal discharges. Secondary tissue impairment observed after traumatic brain injury is also connected with neuronal dysfunction. Those three neurological disorders are ineffectively treated with currently available pharmacotherapy options so great effort is made in searching for new effective drugs. Four N-(E)-cinnamoyl (cinnamamide) derivatives of aminoalkanols: S-(2E)-N-(1-hydroxypropan-2-yl)-3-(2-methylphenyl)prop-2-enamide (1), R,S-(2E)-3-(4-chlorophenyl)-N-(1-hydroxybutan-2-yl)prop-2-enamide (2), R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide (3), (2E)-3-(4-chlorophenyl)-N-(4-hydroxycyclohexyl)prop-2-enamide (4) were evaluated in vivo and in vitro for anticonvulsant, neuroprotective and/or analgesic activity...
April 4, 2019: Bioorganic & Medicinal Chemistry Letters
Danli Zhou, Siqi Zhang, Liang Hu, Yu-Feng Gu, Yimei Cai, Deqin Wu, Wen-Tao Liu, Chun-Yi Jiang, Xiangqing Kong, Guang-Qin Zhang
BACKGROUND: Neuropathic pain is a serious clinical problem that needs to be solved urgently. ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. Therefore, inhibition of ASK1 may be a novel therapeutic approach for neuropathic pain. Here, we aim to investigate the effects of paeoniflorin on ASK1 and neuropathic pain. METHODS: The mechanical and thermal thresholds of rats were measured using the Von Frey test...
April 11, 2019: Journal of Neuroinflammation
Akira Sayo, Hiroyuki Konishi, Masaaki Kobayashi, Kuniyuki Kano, Hiroki Kobayashi, Hideharu Hibi, Junken Aoki, Hiroshi Kiyama
BACKGROUND: Neuropathic pain is caused by sensory nerve injury, but effective treatments are currently lacking. Microglia are activated in the spinal dorsal horn after sensory nerve injury and contribute to neuropathic pain. Accordingly, molecules expressed by these cells are considered potential targets for therapeutic strategies. Our previous gene screening study using a mouse model of motor nerve injury showed that the G-protein-coupled receptor 34 gene (GPR34) is induced by nerve injury...
April 11, 2019: Journal of Neuroinflammation
Tae-Woo Nam, Hyun-Min Oh, Jae-Eun Lee, Ju-Hyun Kim, Jong-Moon Hwang, Eunhee Park, Tae-Du Jung
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains an important therapeutic option for many hematologic malignancies. Bone marrow harvesting from an appropriate donor must be conducted for hematopoietic stem cell transplantation (HSCT). Many previous studies show complications of the recipient after hematopoietic stem cell transplantation (HSCT). However, complications of the donor after bone marrow harvesting are rare. We here report a unique case of a patient who developed sacral nerve root injury after bone marrow harvesting...
April 11, 2019: BMC Cancer
Franziska Karl, Maria B Nandini Colaço, Annemarie Schulte, Claudia Sommer, Nurcan Üçeyler
BACKGROUND: Chronic neuropathic pain is often associated with anxiety, depressive symptoms, and cognitive impairment with relevant impact on patients` health related quality of life. To investigate the influence of a pro-inflammatory phenotype on affective and cognitive behavior under neuropathic pain conditions, we assessed mice deficient of the B7 homolog 1 (B7-H1), a major inhibitor of inflammatory response. RESULTS: Adult B7-H1 ko mice and wildtype littermates (WT) received a chronic constriction injury (CCI) of the sciatic nerve, and we assessed mechanical and thermal sensitivity at selected time points...
April 11, 2019: BMC Neuroscience
Augusto Caraceni, Morena Shkodra
More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional ways of classifying pain in the cancer population include distinguishing pain etiology, clinical characteristics related to pain and the patient, pathophysiology, and the use of already validated classification systems...
April 10, 2019: Cancers
Hiroyuki Ishiguro, Takashi Kaito, Kunihiko Hashimoto, Junichi Kushioka, Rintaro Okada, Hiroyuki Tsukazaki, Joe Kodama, Zeynep Bal, Yuichiro Ukon, Shota Takenaka, Takahiro Makino, Yusuke Sakai, Hideki Yoshikawa
BACKGROUND CONTEXT: Spinal cord injury (SCI) results in not only motor dysfunction but also chronic neuropathic pain. Allodynia, an abnormal sensation that evokes pain against non-noxious stimuli, is a major symptom of post-SCI neuropathic pain. Astrocytic activation is a cause of post-SCI neuropathic pain and is considered a key treatment target. However, no effective treatment for these problems is available to date. ONO-2506 is a novel agent that suppresses astrocytic activation by inhibition of S100B production from astrocytes...
April 8, 2019: Spine Journal: Official Journal of the North American Spine Society
Yohei Tanimura, Masato Yoshida, Masahiro Ohsawa, Toshiaki Makino
ETHNOPHARMACOLOGICAL RELEVANCE: Processed aconite root (PA), the root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. In our previous study, PA and its active ingredient, neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice. AIM OF THE STUDY: The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients...
April 8, 2019: Journal of Ethnopharmacology
Koen P V Meuwissen, Maarten van Beek, Elbert A J Joosten
BACKGROUND: Clinical research suggests that a novel spinal cord stimulation (SCS) waveform, known as Burst-SCS, specifically targets cognitive-motivational aspects of pain. The objective of the present study was to assess the cognitive-motivational aspects of Tonic- and Burst SCS-induced pain relief, by means of exit latency in the mechanical conflict-avoidance system (MCAS), in a rat model of chronic neuropathic pain. METHODS: Exit latency on the MCAS operant testing setup was evaluated at various probe heights for rats (n = 26) with chronic neuropathic pain induced by a partial sciatic nerve ligation (PSNL)...
April 11, 2019: Neuromodulation: Journal of the International Neuromodulation Society
Bogdan Bjelica, Stojan Peric, Ivo Bozovic, Aleksandra Kacar, Mina Cobeljic, Ivana Dejanovic, Zorica Stevic, Ivana Basta
BACKGROUND: We sought to gather information about frequency and features of neuropathic pain (NeP) in CIDP patients and to investigate course of NeP during one-year follow-up. METHODS: Study included 105 patients diagnosed with CIDP. Patients with diabetes (N=26) were excluded. NeP was diagnosed by the official guidelines and painDETECT questionnaire (PD-Q). Medical Research Council Sum Score (MRC-SS), INCAT disability and sensory scores, and Beck Depression Inventory were also measured...
April 11, 2019: Journal of the Peripheral Nervous System: JPNS
Wenli Fang, Wang Liao, Yuqiu Zheng, Xiaoyun Huang, Xueling Weng, Shengnuo Fan, Xiaoyu Chen, Xingmei Zhang, Jianjun Chen, Songhua Xiao, Anderson Thea, Ping Luan, Jun Liu
Alzheimer's disease (AD) is a devastating neurodegenerative disease with limited treatments and no cure. Neurotropin (NTP) is an analgesic drug widely prescribed for neuropathic pain. Increasing evidence suggests that NTP may also protect against neurodegeneration, but NTP's treatment potential against memory impairments of AD remains to be explored. APP/PS1 mice, which model AD, were given NTP for three months then cognitively tested with the Morris water maze. Their Aβ burden, microglial and astrocytic activation, and BDNF levels were compared to untreated controls using immunofluorescent staining...
2019: American Journal of Translational Research
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