EFFECTS OF ELASTOVISCOUS SOLUTIONS OF HYLURONAN DERIVATIVES ON MECHANOTRANSDUCTION

ABSTRACT Sensory endings of nerve fibers signalling joint pain express stretch-activated ion channels which open in response to an increase in membrane tension. These stretch-activated channels have been well characterised in Xenopus laevis oocytes. We have investigated whether hylan solutions of different elastoviscosity used for intra-articular treatment of joint pain in humans, modify the response characteristics of native stretch-activated ion channels of oocytes. Patch-clamp recordings on intact oocytes and in isolated membrane patches (outside-out) were performed in Barth's solution (control condition) and after exposure to hylans of different elastoviscosity. For mechanical stimulation, monitored suction was applied through the microelectrode and the activity of stretch-activated channels was recorded. The activity of the channels was significantly reduced in the presence of high elastoviscous hylan A, 0.9 % polymer content, molecular weight 6 M and of a mixture of hylan A (90% by weight) and hylan B (10% by weight 0.8% total polymer content), labelled as Synvisc®, a clinically used hylan product. In contrast, when a non-elastoviscous solution of hylan (hylan A, molecular weight 96, 000) was used, no effect was observed. In conclusion, stretch-activated channels have a decreased mechanical sensitivity in the presence of elastoviscous solutions of hylan, but not in the presence of non-elastoviscous solutions of hylan of the same concentration. These data suggest that the analgesic effect of intra-articular injection of elastoviscous solutions of hylans are due to a reduction of the sensitivity of joint mechano-nociceptors sensitivity in animals and in arthritic patients.