Article

Spinal neurons that possess the substance P receptor are required for the development of central sensitization

Department of Preventive Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 11/2002; 22(20):9086-98.
Source: PubMed

ABSTRACT In previous studies, we have shown that loss of spinal neurons that possess the substance P receptor (SPR) attenuated pain and hyperalgesia produced by capsaicin, inflammation, and nerve injury. To determine the role of SPR-expressing neurons in modulating pain and hyperalgesia, responses of superficial and deep lumbar spinal dorsal horn neurons evoked by mechanical and heat stimuli and by capsaicin were made after ablation of SPR-expressing neurons using the selective cytotoxin conjugate substance P-saporin (SP-SAP). Morphological analysis and electrophysiological recordings were made after intrathecal infusion of vehicle, saporin alone, or SP-SAP. SP-SAP, but not vehicle or SAP alone, produced an approximately 62% decrease in SPR-expressing neurons in the dorsal horn. Loss of SPR-expressing neurons diminished the responses of remaining neurons to intraplantar injection of capsaicin. Peak responses to 10 microg of capsaicin were approximately 65% lower in animals pretreated with SP-SAP compared with controls. Additionally, sensitization to mechanical and heat stimuli that normally follows capsaicin was rarely observed. Importantly, responses to mechanical and heat stimuli in the absence of capsaicin were not altered after SP-SAP treatment. In addition, nociceptive neurons did not exhibit windup in the SP-SAP-treated group. These results demonstrate that SPR-expressing neurons located in the dorsal horn are a pivotal component of the spinal circuits involved in triggering central sensitization and hyperalgesia. It appears that this relatively small population of neurons can regulate the physiological properties of other nociceptive neurons and drive central sensitization.

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    • "LTP in lamina I neurons induced by HFS of C-fibres depends on coactivation of NMDA receptors by glutamate and neurokinin 1 receptors (NK1-R) by substance P, and resulting activation of T type calcium channels (Ikeda et al., 2003; Heinke et al., 2004; Naka et al., 2013). Substance P acting at NK1-R in the superficial dorsal horn of rats is also essential for central sensitization induced by capsaicin through activation of TRPV1-positive afferents (Nichols et al., 1999; Khasabov et al., 2002; Vierck et al., 2003; Rygh et al., 2006). Because the majority of peptidergic nerve fibres express TRPV1 across species one can assume that in our study, those neurons were eliminated by capsaicin preincubation. "
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    • "y nociceptive signals to medullary and brainstem regions and play a critical role in controlling dorsal horn excitability through a spino - bulbo - spinal facilitatory loop ( Suzuki et al . , 2002 , Suzuki et al . , 2005 ) . Pharmacological elimination of NK1R bearing neurons prevents development of central sensitization ( Nichols et al . , 1999 , Khasabov et al . , 2002 , Suzuki et al . , 2002 , Vierck et al . , 2003 ) . In earlier work we showed that direct activation of NK1R neurons with IT SP induces a centrally - mediated hyperalgesia ( Malmberg and Yaksh , 1992 ) . In the present work , we show that after IT SP , strong pAkt , pmTOR and pS6 expression were detected in dorsal horn neurons labeled wi"
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    • "Substance P interacts with the substance P receptor, also referred to the neurokinin-1 (NK 1 ) receptor to produce its postsynaptic effects. Spinal NK 1 receptor expressing cells plays a critical role in injury-induced hyperalgesia or pain [17] [24] [49] [51]. The physiological significant action of substance P is probably terminated by a membrane-bound protease capable of degrading substance P in the synaptic region. "
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