N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats

Carlsson-Jonsson, AnnaUppsala universitet,Institutionen för farmaceutisk biovetenskap (author)

Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.

Gao, TianleKarolinska Institutet (author)
Hao, Jing-Xia (author)
Fransson, RebeccaUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)refra498 (author)
Sandström, AnjaUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)anjajoha (author)
Nyberg, FredUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)frednybe (author)
Wiesenfeld-Hallin, ZsuzsannaKarolinska Institutet (author)
Xu, Xiao-Jun (author)
Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

In:European Journal of Pharmacology: Elsevier BV738, s. 319-3250014-29991879-0712

By the author/editor: Carlsson-Jonsson ...; Gao, Tianle; Hao, Jing-Xia; Fransson, Rebecc ...; Sandström, Anja; Nyberg, Fred; show more...; Wiesenfeld-Halli ...; Xu, Xiao-Jun; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

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