title: Glutamate, substance P, and calcitonin gene-related peptide cooperate in inflammation-induced heat hyperalgesia.
abstract: The transient receptor potential cation channel subfamily V member 1 (TRPV1) is known as a thermosensor and integrator of inflammation-induced hyperalgesia. TRPV1 is expressed in a subpopulation of primary afferent neurons that express several different neurotransmitters. The role of the TRPV1 channel in the development of hyperalgesia is established, but the role of the neurotransmitter glutamate, used partially by the same neuronal population and thus probably mediating the response, is still under investigation. We have used a Trpv1-Cre mouse line in which we either ablated Trpv1-Cre expressing neurons or induced vesicular glutamate transporter 2 (Vglut2) deficiency in Trpv1-Cre expressing neurons and investigated specific states of hyperalgesia after persistent inflammation. Furthermore, by pharmacologic inhibition of substance P (SP) or calcitonin gene-related peptide (CGRP) signaling in Vglut2-deficient mice, we also evaluated the contribution of SP or CGRP to inflammation-induced hyperalgesia, with or without the presence of vesicular glutamate transporter 2 (VGLUT2)-mediated glutamatergic transmission in Trpv1-Cre neurons. This examination, together with c-Fos analyses, showed that VGLUT2-mediated glutamatergic transmission in Trpv1-Cre afferents together with SP or CGRP is essential for the development of the heat hyperalgesia associated with persistent inflammation. Additionally, SP-, CGRP-, and VGLUT2-mediated transmission together were found to play a role in the development of mechanical hyperalgesia after persistent inflammation.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Rogoz
authors.forename: Helena Haddadi
authors.initials: HH
authors.lastname: Andersen
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
authors.forename: Malin C
authors.initials: MC
authors.lastname: Lagerström
mesh_terms: D000731:Androstanes / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology*; D007249:Inflammation / Q000150:complications*; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D013373:Substance P / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000502:physiology
chemical_list: D000731:Androstanes; D001562:Benzimidazoles; D010879:Piperazines; D011799:Quinazolines; C493477:Slc17a6 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; C086111:WIN 51708; D013373:Substance P; D018698:Glutamic Acid; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant