Local Injection of a Selective Endothelin-B Receptor Agonist Inhibits Endothelin-1-Induced Pain-Like Behavior and Excitation of Nociceptors in a Naloxone-Sensitive Manner

Khodorova, Alla; Fareed, Moin U.; Gokin, A. P.; Strichartz, Gary R.; Davar, Gudarz

doi:10.1523/jneurosci.22-17-07788.2002

Cited by 65 publications

(69 citation statements)

References 45 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding is consistent with previous studies in which C nociceptors in rats were excited by injection of ET-1 (Gokin et al 2001;Khodorova et al 2002) and likely contributes to ET-1-evoked nocifensive behaviors. The latency from the time of injection of ET-1 to excitation of C nociceptors in rats ranged from 1.2 to 5.6 min with a mean of 3.16 Ϯ 0.31 (SE) min (Gokin et al 2001;Khodorova et al 2002). We also observed that the latency to excitation varied between C nociceptors.…”

Section: Et-1-evoked Excitation Of C Nociceptorssupporting

confidence: 93%

“…Recording ongoing activity of C nociceptors at 5 min after injection of ET-1 coincides well with a recent report that pain evoked by ET-1 in humans was maximal between 4 and 5 min after intracutaneous injection (Namer et al 2007). Because the duration of responses to ET-1 of C nociceptors ranged from 15 to 40 min (Gokin et al 2001;Khodorova et al 2002), it is unlikely that many C nociceptors responded to the ET-1 earlier but did not exhibit ongoing activity at 5 min.…”

Section: Et-1-evoked Excitation Of C Nociceptorssupporting

confidence: 88%

“…Numerous studies have demonstrated that injection of ET-1 into the knee or hind paw evokes nocifensive behaviors (Baamonde et al 2004;Balonov et al 2006;De-Melo et al 1998a;Ferreira et al 1989;Gokin et al 2001;McKelvy et al 2007;Menendez et al 2003b;Piovezan et al 1998Piovezan et al , 2004Verri et al 2004Verri et al , 2005, tactile allodynia (Balonov et al 2006;McKelvy et al 2007), and mechanical (da Ferreira et al 1989) and heat (Menendez et al 2003b) hyperalgesia through a mechanism involving the ET A receptors located in peripheral tissues (Baamonde et al 2004;Davar et al 1998;De-Melo et al 1998a;Fareed et al 2000;Gokin et al 2001;Menendez et al 2003b;Piovezan et al 2000). Injection of ET-1 into the skin excites C nociceptors (Gokin et al 2001;Khodorova et al 2002;Namer et al 2007) and likely contributes to ET-1-evoked nocifensive behaviors.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin

Hamamoto

Khasabov

Cain

et al. 2008

Journal of Neurophysiology

View full text Add to dashboard Cite

Hamamoto DT, Khasabov SG, Cain DM, Simone DA. Tumorevoked sensitization of C nonciceptos: a role for endothelin. J Neurophysiol 100: 2300 -2311, 2008. First published August 6, 2008 doi:10.1152/jn.01337.2007. Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to the chronic pain and hyperalgesia accompanying this condition. This study focused on the role of the endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in the process of cancer pain. Electrophysiological response properties, including ongoing activity and responses evoked by heat stimuli, of C nociceptors were recorded in vivo from the tibial nerve in anesthetized control mice and mice exhibiting mechanical hyperalgesia following implantation of fibrosarcoma cells into and around the calcaneus bone. ET-1 (100 M) injected into the receptive fields of C nociceptors innervating the plantar surface of the hind paw evoked an increase in ongoing activity in both control and tumor-bearing mice. Moreover, the selective ET A receptor antagonist, BQ-123 (3 mM), attenuated tumor-evoked ongoing activity in tumor-bearing mice. Whereas ET-1 produced sensitization of C nociceptors to heat stimuli in control mice, C nociceptors in tumor-bearing mice were sensitized to heat, and their responses were not further increased by ET-1. Importantly, administration of BQ-123 attenuated tumor-evoked sensitization of C nociceptors to heat. We conclude that ET-1 at the tumor site contributes to tumor-evoked excitation and sensitization of C nociceptors through an ET A receptor mediated mechanism.

show abstract

Section: Et-1-evoked Excitation Of C Nociceptorssupporting

confidence: 93%

Section: Et-1-evoked Excitation Of C Nociceptorssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin

Hamamoto

Khasabov

Cain

et al. 2008

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…A five-fold increase in endogenous ET-1 is caused by TNF-α, the most rapid inducer of ET-1 (Klemm et al, 1995). IL-1β and IL-1α are known to increase sensory nerve fiber excitability and produce hyperalgesia (Ferreira et al, 1988;Meyer et al, 2006), and these changes may be linked by ET-1 (Khodorova et al, 2002). Therefore, sites of tissue injury have elevated cytokines related to inflammation and these can contribute to endogenous ET-1 release and, by this pathway, to the development of local allodynia.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous endothelin-A receptors elevate post-incisional pain

Mujenda

Duarte

Reilly

et al. 2007

Pain

Self Cite

View full text Add to dashboard Cite

The contribution of endothelin-1 (ET-1), acting via endothelin-A receptors (ET A ), on post-incisional pain was examined in a rat model of incision through the hairy skin of the lumbar dorsum. Postincisional mechanical hyperesthesia was evaluated by cutaneous trunci muscle reflexes (CTMR) of subcutaneous muscles responding to stimulation with von Frey filaments near the wound (primary responses) and at a distance, especially on the contralateral dorsum (secondary responses, involving spinal circuits). The role of ET A was determined by pre-incisional, subcutaneous injection of the selective receptor antagonist BQ-123 at the incision site, 15 min or 24 hr before surgery. Control incisions showed both primary tactile allodynia and hyperalgesia, and a weaker secondary hyperesthesia, peaking 3-4 h after surgery and lasting at least 24h. Primary allodynia, but not hyperalgesia, was dose-dependently suppressed by 15 min pre-incisional BQ-123. In contrast, both secondary allodynia and hyperalgesia were inhibited by local BQ-123. The suppression of primary allodynia by local antagonist disappeared in 24 h, but that of secondary hyperesthesia remained strong for at least 24 h. Systemically delivered BQ-123 was without effect on any post-incisional hyperesthesia, and if the antagonist was locally injected 24 h before surgery there was no difference on hyperesthesia compared to vehicle injected at that time. We conclude that ET-1, released from skin by incision, activates nociceptors to cause primary allodynia and to sensitize spinal circuits through central sensitization. Blockade of ET A in the immediate peri-operative period prevents the later development of central sensitization.

show abstract

“…Endothelin (ET)-1, a known modulator of both nociceptors 12,13 and baroreceptors, 14,15 plays a powerful modulatory role in the activation of renal pelvic mechanosensory nerves. 16 ET-1 exerts its effects by activating 2 G protein-coupled receptors, ETA and ETB receptors (Rs).…”

mentioning

confidence: 99%

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

2007

View full text Add to dashboard Cite

Abstract-Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7Ϯ2% to 15Ϯ2% and the prostaglandin (PG) E 2 -mediated substance P release from 0Ϯ1 to 8Ϯ1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE 2 -mediated release of substance P (17Ϯ3% and 8Ϯ1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123ϩlosartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE 2 -mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27Ϯ4% to 8Ϯ3% and the PGE 2 -mediated substance P release from 9Ϯ0 to 1Ϯ1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE 2 -mediated substance P release toward control (27Ϯ6% and 7Ϯ1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet. Key Words: ETA-receptors Ⅲ AT1-receptors Ⅲ afferent renal nerves Ⅲ PGE 2 Ⅲ substance P Ⅲ BQ123 Ⅲ losartan T he majority of the afferent renal nerves are located in the renal pelvic wall. 1-3 Activation of these nerves by increases in renal pelvic pressure results in increases in afferent renal nerve activity (ARNA) leading to reflex decreases in efferent renal sympathetic nerve activity and diuresis and natriuresis, that is, a renorenal reflex response. 4 Among the various mechanisms activated by stretching the renal pelvic wall is induction of cyclooxygenase-2 resulting in increased renal pelvic synthesis of PGE 2 . 5,6 PGE 2 leads to activation of the cAMP-protein kinase A transduction pathway and a release of the neuropeptide substance P, which activates the afferent renal nerves by stimulating neurokinin-1 receptors in the renal pelvic area. 1,7,8 The responsiveness of the afferent renal nerves is enhanced by high-sodium diet and suppressed by low-sodium diet because of an interaction between prostaglandin (PG) E 2 (PGE 2 ) and angiotensin (Ang) II at the peripheral renal sensory nerve endings. 7,9,10 In conditions of high-sodium diet, characterized by low endogenous Ang II, 11 there is little or no inhibition of the PGE 2 -mediated activation of adenylyl cyclase. Conversely, in conditions of low-sodium diet, ...

show abstract

Local Injection of a Selective Endothelin-B Receptor Agonist Inhibits Endothelin-1-Induced Pain-Like Behavior and Excitation of Nociceptors in a Naloxone-Sensitive Manner

Cited by 65 publications

References 45 publications

Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin

Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin

Cutaneous endothelin-A receptors elevate post-incisional pain

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

Contact Info

Product

Resources

About