Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate pain transmission in conditions such as inflammation, and thereby contribute to hyperalgesia. Since blockade of NK-1 receptors in the RVM can attenuate hyperalgesia produced by prolonged inflammation, we examined the role of NK-1 receptors in changes of response properties of RVM neurons following four days of hind paw inflammation with complete Freund's adjuvant. Recordings were made from functionally identified ON, OFF and NEUTRAL cells in the RVM. Spontaneous activity and responses evoked by a series of mechanical (10, 15, 26, 60, 100, and 180. g) and heat (34-50. °C) stimuli applied to the inflamed and non-inflamed hind paws were determined before and at 15 and 60. min after injection of the NK-1-antagonist L-733,060 or vehicle into the RVM. Prolonged inflammation did not alter the proportions of functionally-identified ON, OFF and NEUTRAL cells. ON cells exhibited enhanced responses to mechanical (60-100. g) and heat (48-50. °C) stimuli applied to the inflamed paw, which were attenuated by L-733,060 but not by vehicle. Inhibitory responses of OFF cells evoked by mechanical stimuli applied to the inflamed paw were also inhibited by L-733,060, but responses evoked by stimulation of the contralateral paw were increased. Heat-evoked responses of OFF cells were not altered by L-733,060. Also, neither L-733,060 nor vehicle altered spontaneous ongoing discharge rate of RVM neurons. These data indicate that NK-1 receptors modulate excitability of ON cells which contribute to both mechanical and heat hyperalgesia, whereas NK-1 modulation of OFF cells contributes to mechanical hyperalgesia during prolonged inflammation.
|Original language||English (US)|
|Number of pages||14|
|State||Published - Nov 8 2012|
Bibliographical noteFunding Information:
The authors thank Drs. Donna Hammond and Darryl Hamamoto for reading an earlier version of the manuscript. This work was supported by NIH grants DA011471 and CA091007 (D.A. Simone), and DA023576 (D.L. Hammond). T.S. Brink was supported by the National Institute of Dental and Craniofacial Research ( T32-DE007288 ).
Copyright 2013 Elsevier B.V., All rights reserved.
- Descending facilitation
- Inflammatory pain
- Rostral ventromedial medulla