NIUROSCIEHCi ELSEVIER Neuroscience Letters 203 (1996) 119-122 LEITERS Influence of inflammation or disconnection from peripheral target tissue on the capsaicin sensitivity of rat dorsal root ganglion sensory neurones Mi Hu-Tsai a,l, Clifford Woolf b, Janet Winter ~,* aSandoz Institute for Medical Research, 5 Cower Place, London WC1E 6BN, UI( bThomas Lewis Pain Research Centre, University College London, Gower Street, London WC1E 6BT, UK Received6 November1995;revised versionreceived 6 December1995;accepted 6 December1995 Abstract Dorsal root ganglion (DRG) sensory neurones from adult rats are known to lose their capsaicin sensitivity in vitro if they are cul- tured without nerve growth factor (NGF). Here we show similar results following peripheral nerve transection in vivo, which deprives DRG sensory neurones of target-derived NGF. By measuring capsaicin-stimulated 45Ca uptake into DRG neurones which had been briefly cultured, capsaicin sensitivity was shown to decrease in neurones whose axons had been previously severed in vivo. Conversely, during experimental inflammation of the rat paw, there is an increase in the supply of NGF to neurones innervating the inflamed area. In this case, however, no significant increase in capsaicin sensitivity could be demonstrated in briefly cultured neurones which had previously innervated an inflamed limb. This suggests that expression of capsaicin sensitivity in DRG is maximal at levels of NGF found in normal animals. Keywords: Capsaicin-sensitivity; Dorsal root ganglion; Sensory neurones; Inflammation; Axotomy The hot ingredient of chilli peppers, capsaicin, selec- tively stimulates a subset of dorsal root ganglion sensory neurones by opening a non-selective cation channel in their cell membranes [4,15,18]. Capsaicin can have re- versible effects; it excites sensory neurones, causing a painful sensation, and it desensitizes, reducing pain sen- sation to further noxious stimuli [18]. Additionally, at higher concentrations capsaicin causes irreversible toxic effects, resulting in neuronal damage or death [20]. The same receptor/channel complex that is activated by capsa- icin is also activated by low pH (protons) which may be the endogenous mediator(s) of the activity of this channel [1,2]. In some inflammatory and ischaemic conditions the pH of the tissue fluids may drop into the range that can activate these channels [2,14] and channel density in the neurones supplying these tissues may therefore be impor- tant in transmission of noxious stimuli. The expression of capsaicin and proton sensitivity in * Corresponding author. Tel.: +44 171 3332155; fax: +44 171 3874116;e-mail: winter@sandoz.com. 1 Currentaddress: Flat 5, Floor 14, No. 63 Lane 122, Section4, Jew Ai Road, Taipei,Taiwan. cultured sensory neurones from rat dorsal root ganglia (DRG) requires the continued presence of nerve growth factor (NGF) in the growth medium [1,19]. Moreover, a recent study has shown that chronic (2 week) NGF deple- tion in vivo using a chimeric trkA-IgG fusion protein (the extracellular domain of the NGF receptor fused to immu- noglobulin) to sequester endogenous NGF, causes a re- duced sensitivity to intradermal capsaicin [11]. Systemic treatment of adult rats with high doses (50 mg/kg) of capsaicin also results in decreased DRG neurone capsaicin sensitivity 2 weeks later [19]. This may be due to disruption of contact with target tissue, as DRG sensory neurones react to this capsaicin treatment in a similar manner to surgically axotomized neurones, by increasing growth-associated protein-43 (GAP-43) pro- duction and producing rapid neurite outgrowth when dis- sociated and grown in culture [17,19]. Decreased capsa- icin sensitivity can be demonstrated by both radioligand binding and by autoradiographic localization of a potent capsaicin analogue, resiniferatoxin (RTX) [19]. There is a decrease in both the number of ligand binding sites in DRG membranes and the amount of labelling in cryostat sections of the dorsal horn and DRG in tissue from capsa- 0304-3940/96/$12.00 © 1996ElsevierScienceIrelandLtd. All fightsreserved SSD! 0304-3940(95)12277-8