Increased neuronal expression of neurokinin‐1 receptor and stimulus‐evoked internalization of the receptor in the rostral ventromedial medulla of the rat after peripheral inflammatory injury

Hamity, Marta V.; Walder, Roxanne Y.; Hammond, Donna L.

doi:10.1002/cne.23564

Cited by 8 publications

(14 citation statements)

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“…Total RNA was extracted from the RVM and the ipsilateral and contralateral PAG of saline- and CFA-treated rats using the Qiagen RNeasy lipid tissue mini kit (Qiagen, Valencia, CA) as previously described (Hamity et al, 2014). Sufficient quantities of RNA could be isolated from single punches of RVM and PAG tissue for multiple analyses.…”

Section: Methodsmentioning

confidence: 99%

“…For this study, five to six 50-μm coronal sections spanning the rostral–caudal extent of the RVM were obtained for each rat in the six treatment groups. The optical fractionator probe of Stereoinvestigator software (Microbrightfield Bioscience, Colchester, VT) was used to randomly sample the regions of interest within the RVM as previously described (Hamity et al, 2014). Briefly, a rectangle was centered over the RVM with the top edge aligned with the dorsal edge of the facial nucleus, the base at the dorsal edge of the pyramidal tracts and the lateral edges aligned with the lateral edge of the pyramids.…”

Section: Methodsmentioning

confidence: 99%

“…The mechanisms by which it acts in the periphery and spinal cord to induce and maintain heat hyperalgesia and mechanical hypersensitivity after peripheral inflammatory injury are well characterized (see reviews by (Baranauskas and Nistri, 1998; Sandkuhler et al, 2000; Snijdelaar et al, 2000; Mantyh, 2002; Keeble and Brain, 2004; Seybold, 2009; Todd, 2010; Steinhoff et al, 2014). Our understanding of its actions within supraspinal nuclei that modulate the transmission of nociceptive information in the spinal cord continues to evolve, particularly with respect to its actions in the rostral ventromedial medulla (RVM) (Lagraize et al, 2010; Hahm et al, 2011; Brink et al, 2012; Khasabov and Simone, 2013; Hamity et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

“…The RVM contains high concentrations of SubP that originate from neurons located in the nucleus cuneiformis, dorsal raphe nucleus, and periaqueductal gray (PAG) (Beitz, 1982; Chen et al, 2013), as well as a moderate density of neurokinin-1 receptors (NK1R) at which SubP exerts its actions (Saffroy et al, 1988; Nakaya et al, 1994; Hamity et al, 2014). In uninjured animals, a single injection or continuous infusion of SubP into the RVM causes hypersensitivity of the hindpaw to noxious heat stimuli that can last 24 hours (Hamity et al, 2010; Lagraize et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Previous work documented that NK1R is upregulated in the RVM as early as two hours to four days after peripheral inflammatory injury (Lagraize et al, 2010; Hamity et al, 2014). Also, the number of neurons that express NK1R is increased four days after intraplantar injection of CFA (Hamity et al, 2014). However, whether a corresponding increase in the levels or change in the disposition of SubP, the endogenous ligand for NK1R, occurs in the RVM following inflammatory injury is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the disposition of substance P in the rostral ventromedial medulla after inflammatory injury in the rat

et al. 2016

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This study examined whether peripheral inflammatory injury increases the levels or changes the disposition of substance P (SubP) in the rostral ventromedial medulla (RVM), which serves as a central relay in bulbospinal pathways of pain modulation. Enzyme immunoassay and reverse transcriptase quantitative polymerase chain reaction were used to measure SubP protein and transcript, respectively, in tissue homogenates prepared from the RVM and the periaqueductal gray and cuneiform nuclei of rats that had received an intraplantar injection of saline or complete Freund's adjuvant (CFA). Matrix Assisted Laser Desorption/Ionization Time of Flight analysis confirmed that the RVM does not contain hemokinin-1, which can confound measurements of SubP because it is recognized equally well by commercial antibodies for SubP. Levels of SubP protein in the RVM were unchanged four hours, four days and two weeks after injection of CFA. Tac1 transcripts were similarly unchanged in the RVM four days or two weeks after CFA. In contrast, the density of SubP immunoreactive processes in the RVM increased 2-fold within four hours and 2.7-fold four days after CFA injection; it was unchanged at two weeks. SubP-immunoreactive processes in the RVM include axon terminals of neurons located in the periaqueductal gray and cuneiform nucleus. Substance P content in homogenates of the periaqueductal gray and cuneiform nucleus was significantly increased four days after CFA, but not at four hours or two weeks. Tac1 transcripts in homogenates of these nuclei were unchanged four days and two weeks after CFA. These findings suggest that there is an increased mobilization of SubP within processes in the RVM shortly after injury accompanied by an increased synthesis of SubP in neurons that project to the RVM. These findings are consonant with the hypothesis that an increase in SubP release in the RVM contributes to the hyperalgesia that develops after peripheral inflammatory injury.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%