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Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM.
J Neurophysiol. 2003 Oct; 90(4):2702-10.JN

Abstract

It is well established that the vanilloid receptor, VR1, is an important peripheral mediator of nociception. VR1 receptors are also located in several brain regions, yet it is uncertain whether these supraspinal VR1 receptors have any influence on the nociceptive system. To investigate a possible nociceptive role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 microl) was microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion in 52 degrees C water) and on neuronal activity (on-, off-, and neutral cells) in the rostral ventromedial medulla (RVM) were measured in lightly anesthetized rats. Administration of capsaicin into the dPAG but not the vPAG caused an initial hyperalgesic response followed later by analgesia (125 +/- 20.96 min postinjection). The tail flick-related burst in on-cell activity was triggered earlier in the hyperalgesic phase and was delayed or absent during the analgesic phase. Spontaneous activity of on-cells increased at the onset of the hyperalgesic phase and decreased before and during the analgesic phase. The tail flick-related pause in off-cell activity as well as spontaneous firing for these cells was unchanged in the hyperalgesic phase. During the analgesic phase, off-cells no longer paused during noxious stimulation and had increased levels of spontaneous activity. Neutral cell firing was unaffected in either phase. Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4 microl), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the corresponding changes in on- and off-cell activity. VR1 receptor immunostaining was observed in the dPAG of untreated rats. Microinjection of capsaicin likely sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and RVM neuronal activity. These results suggest that supraspinal VR1 receptors in the dPAG contribute to descending modulation of nociception.

Authors+Show Affiliations

Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. Steve.P.McGaraughty@abbott.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12815018

Citation

McGaraughty, Steve, et al. "Capsaicin Infused Into the PAG Affects Rat Tail Flick Responses to Noxious Heat and Alters Neuronal Firing in the RVM." Journal of Neurophysiology, vol. 90, no. 4, 2003, pp. 2702-10.
McGaraughty S, Chu KL, Bitner RS, et al. Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM. J Neurophysiol. 2003;90(4):2702-10.
McGaraughty, S., Chu, K. L., Bitner, R. S., Martino, B., El Kouhen, R., Han, P., Nikkel, A. L., Burgard, E. C., Faltynek, C. R., & Jarvis, M. F. (2003). Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM. Journal of Neurophysiology, 90(4), 2702-10.
McGaraughty S, et al. Capsaicin Infused Into the PAG Affects Rat Tail Flick Responses to Noxious Heat and Alters Neuronal Firing in the RVM. J Neurophysiol. 2003;90(4):2702-10. PubMed PMID: 12815018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM. AU - McGaraughty,Steve, AU - Chu,Katharine L, AU - Bitner,Robert S, AU - Martino,Brenda, AU - El Kouhen,Rachid, AU - Han,Ping, AU - Nikkel,Arthur L, AU - Burgard,Edward C, AU - Faltynek,Connie R, AU - Jarvis,Michael F, Y1 - 2003/06/18/ PY - 2003/6/20/pubmed PY - 2004/1/6/medline PY - 2003/6/20/entrez SP - 2702 EP - 10 JF - Journal of neurophysiology JO - J Neurophysiol VL - 90 IS - 4 N2 - It is well established that the vanilloid receptor, VR1, is an important peripheral mediator of nociception. VR1 receptors are also located in several brain regions, yet it is uncertain whether these supraspinal VR1 receptors have any influence on the nociceptive system. To investigate a possible nociceptive role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 microl) was microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion in 52 degrees C water) and on neuronal activity (on-, off-, and neutral cells) in the rostral ventromedial medulla (RVM) were measured in lightly anesthetized rats. Administration of capsaicin into the dPAG but not the vPAG caused an initial hyperalgesic response followed later by analgesia (125 +/- 20.96 min postinjection). The tail flick-related burst in on-cell activity was triggered earlier in the hyperalgesic phase and was delayed or absent during the analgesic phase. Spontaneous activity of on-cells increased at the onset of the hyperalgesic phase and decreased before and during the analgesic phase. The tail flick-related pause in off-cell activity as well as spontaneous firing for these cells was unchanged in the hyperalgesic phase. During the analgesic phase, off-cells no longer paused during noxious stimulation and had increased levels of spontaneous activity. Neutral cell firing was unaffected in either phase. Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4 microl), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the corresponding changes in on- and off-cell activity. VR1 receptor immunostaining was observed in the dPAG of untreated rats. Microinjection of capsaicin likely sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and RVM neuronal activity. These results suggest that supraspinal VR1 receptors in the dPAG contribute to descending modulation of nociception. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/12815018/Capsaicin_infused_into_the_PAG_affects_rat_tail_flick_responses_to_noxious_heat_and_alters_neuronal_firing_in_the_RVM_ L2 - https://journals.physiology.org/doi/10.1152/jn.00433.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -