title: N-terminal truncations of substance P 1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats.
abstract: 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 biodistribution and stability of the peptides. Most of the examined compounds alleviated mechanical allodynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by any of the compounds tested. Most of the amino acids in the heptapeptide structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapeptide and its N-terminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden. Electronic address: anna.jonsson@farmbio.uu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Carlsson-Jonsson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
authors.forename: Tianle
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
authors.forename: Jing-Xia
authors.initials: JX
authors.lastname: Hao
authors.affiliation: Department of Medicinal Chemistry, Uppsala University, P.O. Box 574, SE-751 24 Uppsala, Sweden.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fransson
authors.affiliation: Department of Medicinal Chemistry, Uppsala University, P.O. Box 574, SE-751 24 Uppsala, Sweden.
authors.forename: Anja
authors.initials: A
authors.lastname: Sandström
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
mesh_terms: D000577:Amides / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D013329:Structure-Activity Relationship; D013373:Substance P / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000577:Amides; D010446:Peptide Fragments; D013373:Substance P; C036877:substance P (1-7)
keywords: Anti-allodynia; Chronic pain; Neuropathic pain; Spinal cord injury; Substance P (PubChem CID: 36511); Substance P fragment SP(1–7); Substance P(1–7) (PubChem CID: 115322); Substance P-cleaving enzymes