Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats

Carstens, Earl; Carstens, Mirela Iodi; Simons, Christopher T.; Jinks, Steven L.

doi:10.1097/wnr.0b013e328337310a

Cited by 119 publications

(100 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A), and the mean number of scratch bouts was virtually identical (Fig. lA), such that the mean duration of individual scratch bouts after morphine (2.87 s) was similar to that after naltrexone (2.89 s) and slightly but not significantly different compared to vehicle controls (2.45 s), in agreement with previous reports (8,12,13).…”

Section: Parametric Analysis Of 5-ht-evoked Hindlimb Scratching and Osupporting

confidence: 91%

Opioid Modulation of Facial Itch- and Pain-related Responses and Grooming Behavior in Rats

Spradley¹,

Davoodi²,

Carstens³

et al. 2012

Acta Derm Venerol

View full text Add to dashboard Cite

Intradermal facial injections of pruritogens or algogens elicit distinct behavioral hindlimb scratch or forelimb wiping responses in rodents. We systematically investigated the parameters and opioid modulation of these evoked behaviors and spontaneous facial grooming in rats. Serotonin (5-HT) elicited hindlimb scratch bouts with few wipes. Scratching was attenuated by the µ-opiate antagonist naltrexone but not morphine. In contrast, cheek injection of mustard oil (allyl-isothiocyanate (AITC)) elicited ipsilateral forelimb wipes but little hindlimb scratching. AITC-evoked wiping was significantly attenuated by morphine but not naltrexone. Spontaneous facial grooming by the forepaws was attenuated by naltrexone, whereas morphine did not affect grooming behavior before or after cheek injections of 5-HT or AITC. These data validate that the rodent "cheek" model discriminates between itch- and pain-related behaviors. Naltrexone sensitivity of facial grooming and 5-HT-evoked scratch-ing suggests a common functionality. Forelimb wipes may represent a nocifensive response akin to rubbing an injury to relieve pain.

show abstract

Section: Parametric Analysis Of 5-ht-evoked Hindlimb Scratching and Osupporting

confidence: 91%

Opioid Modulation of Facial Itch- and Pain-related Responses and Grooming Behavior in Rats

Spradley¹,

Davoodi²,

Carstens³

et al. 2012

Acta Derm Venerol

View full text Add to dashboard Cite

show abstract

“…Loss of vesicular glutamate transporter-2 in nociceptors results in reduced pain but enhanced itch, indicating that glutamate release from these nociceptors is dispensable for itch in the absence of pain (41). At the spinal cord level, the peptides GRP and SP, released from TRPV1-expressing nociceptors, activate GRP receptor and NK1 to elicit pruritus (28,31,42). In this study, we further revealed TLR3 as a new player in itch control, to our knowledge, via its peripheral and central actions.…”

Section: Discussionmentioning

confidence: 70%

TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice

Liu¹,

Berta²,

Xu³

et al. 2012

J. Clin. Invest.

148

173

View full text Add to dashboard Cite

Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3 −/− mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3 −/− mice but not Tlr7 −/− mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3 −/− mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3 −/− mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.

show abstract

“…Current evidence indicates that gastrin-releasing peptide (Sun and Chen 2007;Sun et al 2009) and substance P (Carstens et al 2010) may play important roles in the transmission of itch signals from pruriceptors to superficial dorsal horn neurons. Future studies should address possible mechanisms by which primary afferents might be differentially sensitized under pathophysiological conditions associated with chronic itch.…”

Section: Discussionmentioning

confidence: 98%

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model

Akiyama

Carstens

2011

Journal of Neurophysiology

Self Cite

View full text Add to dashboard Cite

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.

show abstract

Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats

Cited by 119 publications

References 24 publications

Opioid Modulation of Facial Itch- and Pain-related Responses and Grooming Behavior in Rats

Opioid Modulation of Facial Itch- and Pain-related Responses and Grooming Behavior in Rats

TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model

Contact Info

Product

Resources

About