Antinociceptive Effects of Aaptamine, a Sponge Component, on Peripheral Neuropathy in Rats

Author:

Sung Chun-Sung12,Cheng Hao-Jung3ORCID,Chen Nan-Fu45,Tang Shih-Hsuan1,Kuo Hsiao-Mei3ORCID,Sung Ping-Jyun367ORCID,Chen Wu-Fu38,Wen Zhi-Hong3ORCID

Affiliation:

1. Department of Anesthesiology, Division of Pain Management, Taipei Veterans General Hospital, Taipei 112201, Taiwan

2. School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan

3. Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804201, Taiwan

4. Department of Surgery, Division of Neurosurgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 802301, Taiwan

5. Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 804201, Taiwan

6. National Museum of Marine Biology and Aquarium, Pingtung 944401, Taiwan

7. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807378, Taiwan

8. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan

Abstract

Aaptamine, a natural marine compound isolated from the sea sponge, has various biological activities, including delta-opioid agonist properties. However, the effects of aaptamine in neuropathic pain remain unclear. In the present study, we used a chronic constriction injury (CCI)-induced peripheral neuropathic rat model to explore the analgesic effects of intrathecal aaptamine administration. We also investigated cellular angiogenesis and lactate dehydrogenase A (LDHA) expression in the ipsilateral lumbar spinal cord after aaptamine administration in CCI rats by immunohistofluorescence. The results showed that aaptamine alleviates CCI-induced nociceptive sensitization, allodynia, and hyperalgesia. Moreover, aaptamine significantly downregulated CCI-induced vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), and LDHA expression in the spinal cord. Double immunofluorescent staining showed that the spinal VEGF and LDHA majorly expressed on astrocytes and neurons, respectively, in CCI rats and inhibited by aaptamine. Collectively, our results indicate aaptamine’s potential as an analgesic agent for neuropathic pain. Furthermore, inhibition of astrocyte-derived angiogenesis and neuronal LDHA expression might be beneficial in neuropathy.

Funder

National Science and Technology Council

Chang Gung Memorial Hospital

Publisher

MDPI AG

Subject

Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science

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