title: Differential sensitization of amygdala neurons to afferent inputs in a model of arthritic pain.
abstract: Pain is associated with negative affect such as anxiety and depression. The amygdala plays a key role in emotionality and has been shown to undergo neuroplastic changes in models of affective disorders. Many neurons in the central nucleus of the amygdala (CeA) are driven by nociceptive inputs, but the role of the amygdala in persistent pain states is not known. This study is the first to address nociceptive processing by CeA neurons in a model of prolonged pain. Extracellular single-unit recordings were made from 41 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Background activity, receptive field size, and threshold were mapped, and stimulus-response functions were constructed. These parameters were measured repeatedly before and after induction of arthritis in one knee by intraarticular injections of kaolin and carrageenan. Multireceptive (MR) amygdala neurons (n = 20) with excitatory input from the knee joint responded more strongly to noxious than to innocuous mechanical stimuli of deep tissue (n = 20) and skin (n = 11). After induction of arthritis, 18 of 20 MR neurons developed enhanced responses to mechanical stimuli and expansion of receptive field size. These changes occurred with a biphasic time course (early peak: 1-1.5 h; persistent plateau phase: after 3-4 h). Responses to thermal stimuli did not change (7 of 7 neurons), but background activity (16 of 18 neurons) and electrically evoked orthodromic activity (11 of 12 neurons) increased in the arthritic state. Nociceptive-specific (NS) neurons (n = 13) showed no changes of their responses to mechanical, thermal, and electrical stimulation after induction of arthritis. A third group of neurons did not respond to somesthetic stimuli under control conditions (noSOM neurons; n = 8) but developed prolonged responses to mechanical, but not thermal, stimuli in arthritis (5 of 8 neurons). These data suggest that prolonged pain is accompanied by enhanced responsiveness of a subset of CeA neurons. Their sensitization to mechanical, but not thermal, stimuli argues against a nonspecific state of hyperexcitability. MR neurons could serve to integrate and evaluate information in the context of prolonged pain. Recruitment of noSOM neurons increases the gain of amygdala processing. NS neurons preserve the distinction between nociceptive and nonnociceptive inputs.
authors.affiliation: Department of Anatomy and Neurosciences and Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA. voneugeb@utmb.edu
authors.forename: Volker
authors.initials: V
authors.lastname: Neugebauer
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
mesh_terms: D000679:Amygdala / Q000166:cytology*; D000818:Animals; D001168:Arthritis / Q000150:complications*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D006358:Hot Temperature; D007719:Knee Joint; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D011149:Pons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation