| Title |
Neurotropin® Ameliorates Chronic Pain via Induction of Brain-Derived Neurotrophic Factor
|
|---|---|
| Published in |
Cellular and Molecular Neurobiology, October 2014
|
| DOI | 10.1007/s10571-014-0118-x |
| Pubmed ID | |
| Authors |
Toshizo Ishikawa, Seiko Yasuda, Seiji Minoda, Takae Ibuki, Kayoko Fukuhara, Yasutake Iwanaga, Toru Ariyoshi, Hironori Sasaki |
| Abstract |
Neurotropin (NTP)(®), a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, is used clinically for the treatment of neuropathic pain. Moreover, NTP may activate the descending pain inhibitory system. Depression-like behavior is often complicated by chronic pain. However, little is known about NTP-mediated prevention of mood disorders in chronic pain and its molecular mechanisms. We aimed to investigate the effects of NTP on brain-derived neurotrophic factor (BDNF)-mediated signaling and gene expression in chronic pain. In addition, these effects of NTP were compared with pregabalin which is an anticonvulsant, anxiolytic analgesic used to treat neuropathic pain and fibromyalgia. A chronic constriction injury model was established in Sprague-Dawley rats. The pain response was assessed using a paw withdrawal latency (PWL) test and depression was assessed by the immobility time in a forced swim test (FST). NTP was orally administered in two doses of 50 NU (Neurotropin Unit) and 100 NU/kg for 7 days from day 7 after injury. To measure the analgesic and anti-depressant effects of NTP, either K252a (a tyrosine kinase inhibitor), or 5,7-dihydroxy tryptamine (5,7-DHT, a selective toxin for 5-HTergic neurons) was administered by intracerebroventricular injection. Changes in pERK1/2 and pCREB (immunohistochemistry), 5-HT, and BDNF protein level (ELISA) and BDNF mRNA (RT-PCR) were measured in the anterior cingulate cortex (ACC) and in the rostral ventromedial medulla (RVM) 14 days after injury. After injury, the rats showed a decrease in PWL associated with the increase in time of immobility in FST. In this injury model, NTP blocked both the decrease in PWL and the increase in the FST, while pregabalin (10 mg/kg, po.) did not affect the increase in the FST. These effects of NTP were reversed by K252a, and 5,7-DHT. The analgesic effects of pregabalin were not reversed by K252a. NTP normalized the injury-induced excessive activation of pERK1/2 associated with decreased pCREB and BDNF mRNA in the ACC and in the RVM, and these changes were reversed by 5,7-DHT. In contrast, pregabalin did not affect either pCREB or BDNF levels in the chronic pain model. NTP ameliorated chronic pain and pain-related depression by normalizing the induction of BDNF associated with the 5-HTergic system. Pregabalin showed the analgesic effects but had no effects on either depression or the BDNF pathway. These results suggest that NTP may represent an additional drug strategy for chronic pain associated with depression. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 2 | 29% |
| Turkey | 1 | 14% |
| Unknown | 4 | 57% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 63 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 12 | 19% |
| Student > Doctoral Student | 8 | 13% |
| Researcher | 7 | 11% |
| Student > Master | 7 | 11% |
| Student > Ph. D. Student | 5 | 8% |
| Other | 12 | 19% |
| Unknown | 12 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 24% |
| Psychology | 8 | 13% |
| Neuroscience | 5 | 8% |
| Nursing and Health Professions | 5 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
| Other | 9 | 14% |
| Unknown | 17 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 January 2020.
All research outputs
#7,399,510
of 24,364,603 outputs
Outputs from Cellular and Molecular Neurobiology
#328
of 1,058 outputs
Outputs of similar age
#75,129
of 259,097 outputs
Outputs of similar age from Cellular and Molecular Neurobiology
#2
of 21 outputs
Altmetric has tracked 24,364,603 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 1,058 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one has gotten more attention than average, scoring higher than 68% of its peers.
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We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.