Abstract: This invention relates generally to compositions and methods for preventing, reducing the occurrence of or treating a headache in a subject in need thereof. In particular, the present invention relates to methods for enhancing 2-arachydonyl glycerol (2AG) tone and reducing prostaglandin activity in a subject for purposes of preventing, reducing the occurrence of or treating a headache (e.g., a migraine headache) in a subject.

Abstract: Disclosed herein are isolated polypeptides capable of preventing collapsin response mediator protein 2 (CRMP2)-small ubiquitin-like modifier (SUMO)ylation mediated trafficking of voltage gated sodium channel 1.7 (Nav1.7) function. In some examples, the disclosed peptides comprise three to twenty amino acids and include the amino acid sequence KMD. Also disclosed are methods of decreasing nociception including administering an effective amount of one or more disclosed peptides to a subject in need thereof, such as a subject experiencing chronic pain.

Abstract: Disclosed herein are isolated polypeptides capable of preventing collapsin response mediator protein 2 (CRMP2)-small ubiquitin-like modifier (SUMO)ylation mediated trafficking of voltage gated sodium channel 1.7 (Nav1.7) function. In some examples, the disclosed peptides comprise three to twenty amino acids and include the amino acid sequence KMD. Also disclosed are methods of decreasing nociception including administering an effective amount of one or more disclosed peptides to a subject in need thereof, such as a subject experiencing chronic pain.

Abstract: The present invention features animal models of migraine pain that can be used in a variety of ways, e.g., to identify compounds that reduce migraine pain or other migraine symptoms, to investigate behavioral changes correlated with the development and maintenance of a migraine-like state, and to better understand the mechanisms that underlie migraine pain.

Abstract: Certain peptides which exhibit high selectivity for the kappa opioid receptor (KOR) versus the mu opioid receptor and little or no CYP3A4 inhibitory activity including tetrapeptides of four D-isomer amino acid residues having a C-terminus which is an N-oxide-substituted amide such, as H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-picolyl-N-oxide.

Abstract: Peptides which exhibit high selectivity for the kappa opioid receptor (KOR) and long duration of peripheral action without significant entry into the brain are created which are sequences of four D-isomer amino acid residues having a C-terminus which is a mono or di-substituted amide. Representative compounds, which have an affinity for the KOR at least 1,000 times their affinity for the mu opioid receptor and an ED.sub.50 of not greater than about 0.5 mg/kg, includeH-D-Phe-D-Phe-D-Nle-D-Arg-NHEt,H-D-Phe-D-Phe-D-Nle-D-Arg-morpholinyl,H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-picolyl,H-D-Phe-D-Phe-D-Nle-D-Arg-NHPr,H-D-Phe-D-Phe-D-Nle-D-Arg-thiomorpholinyl,H-D-Phe-D-Phe-D-Nle-D-Arg-NEt.sub.2,H-D-Phe-D-Phe-D-Nle-D-Arg-NHMe,H-D-Phe-D-Phe-D-Leu-D-Orn-morpholinyl,H-D-Phe-D-Phe-D-Nle-D-Arg-NHhEt,H-D-Phe-D-Phe-D-Nle-D-Arg-NH-cyclopropyl,H-D-Ala(2Thi)-D-4Cpa-D-Leu-D-Arg-morpholinyl,H-D-Phe-D-Phe-D-Nle-D-Arg-piperidinyl,H-D-Phe-D-Phe-D-Leu-D-Orn-NHEt,H-D-Phe-D-Phe-D-Leu-D-Lys-morpholinyl,andH-D-Phe-D-Phe-D-Nle-D-Arg-piperazinyl.