There is a huge need for pharmaceutical agents for the treatment of chronic Neuropathic
Pain (NP), a complex condition where patients can suffer from either hyperalgesia or
allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines
include the use of tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors
and anticonvulsants, beside the use of natural compounds and non-pharmacological options.
Unfortunately, these drugs suffer from limited efficacy and serious dose-dependent adverse
effects. In the last decades, the heptapeptide SP1-7, the major bioactive metabolite produced by
Substance P (SP) cleavage, has been extensively investigated as a potential target for the development
of novel peptidomimetic molecules to treat NP. Although the physiological effects
of this SP fragment have been studied in detail, the mechanism behind its action is not fully
clarified and the target for SP1-7 has not been identified yet. Nevertheless, specific binding
sites for the heptapeptide have been found in brain and spinal cord of both mouse and rats.
Several Structure-Affinity Relationship (SAR) studies on SP1-7 and some of its synthetic analogues
have been carried out aiming to developing more metabolically stable and effective
small molecule SP1-7-related amides that could be used as research tools for a better understanding
of the SP1-7 system and, in a longer perspective, as potential therapeutic agents for
future treatment of NP.