Hyperacusis in patients with complex regional pain syndrome related dystonia.

INTRODUCTION: In complex regional pain syndrome type 1 (CRPS-1), patients may have manifestations of central involvement, including allodynia, hyperalgesia or dystonia. We noted that more severely affected patients may experience hyperacusis, which may also reflect central involvement. The aim of this study was to evaluate the occurrence and characteristics of hyperacusis in patients with CRPS related dystonia. METHODS: The presence of hyperacusis, speech reception thresholds (SRT), pure-tone thresholds (PTT) and uncomfortable loudness (UCL) was evaluated in 40 patients with CRPS related dystonia. RESULTS: PTT and SRT were normal for all patients. 15 patients (38%) reported hyperacusis and this was associated with allodynia/hyperalgesia and with more affected extremities. UCLs of patients with hyperacusis were significantly lower than UCLs of patients without hyperacusis. CONCLUSION: Hyperacusis is common among severely affected patients with CRPS related dystonia and may indicate that the disease spreads beyond those circuits related to sensory-motor processing of extremities.

Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics.

1. Muscarinic m1 receptors are inhibited by local anaesthetics (LA) at nM concentrations. To elucidate in more detail the site(s) of LA interaction, we compared these findings with LA effects on m3 muscarinic receptors. 2. We expressed receptors in Xenopus oocytes. Using two-electrode voltage clamp, we measured the effects of lidocaine, QX314 (permanently charged) and benzocaine (permanently uncharged) on Ca(2+)-activated Cl(-)-currents (I(Cl(Ca))), elicited by acetyl-beta-methylcholine bromide (MCh). We also characterized the interaction of lidocaine with [(3)H]-quinuclydinyl benzylate ([(3)H]-QNB) binding to m3 receptors. Antisense-injection was used to determine the role of specific G-protein alpha subunits in mediating the inhibitory effects of LA. Using chimeric receptor constructs we investigated which domains of the muscarinic receptors contribute to the binding site for LA. 3. Lidocaine inhibited m3-signalling in a concentration-dependent, reversible, non-competitive manner with an IC(50) of 370 nM, approximately 21 fold higher than the IC(50) (18 nM) reported for m1 receptors. Intracellular inhibition of both signalling pathways by LA was similar, and dependent on the G(q)- protein alpha subunit. In contrast to results reported for the m1 receptor, the m3 receptor lacks the major extracellular binding site for charged LA. The N-terminus and third extracellular loop of the m1 muscarinic receptor molecule were identified as requirements to obtain extracellular inhibition by charged LA.