Does Hyaluronidase Enhance Drug Penetration to Mechanoreceptors?

Background: The pharmacological study of mechanoreceptors embedded within tissue is hampered by tissue barriers to applied research drugs. Methods: Hyaluronidase increases the permeability of tissues and is used clinically to facilitate the distribution of injected drugs. An in vitro rat sinus hair preparation was used to determine whether hyaluronidase (1,500 or 3,000 IU/10 mL) had an effect on drug access to receptor sites on slowly adapting St I and St II mechanoreceptors. Electrical recordings were made from single mechanoreceptor units that were activated by trapezoid ramp stimuli. Cinnamaldehyde (500-1,500 mu M) and capsazepine (100 mu M) were used as test drugs. Changes in onset time and degree of depression of firing due to test drugs were compared to control experiments not employing hyaluronidase. Results: There were no statistical effects on any of the observed measures. Often the effects were opposite to those predicted. Using a likelihood approach, it was calculated that there was strong evidence (log-likelihood ratios from -0.5 to -6.5) to support a null effect over a facilitatory effect. There was no evidence of loss of integrity of mechanoreceptor mechanotransduction mechanisms following hyaluronidase applications. Comparison with Existing Method: The use of hyaluronidase does not facilitate drug access to receptors. Conclusions: In the in vitro sinus hair preparation, the addition of hyaluronidase does not allow easier access to slowly adapting mechanoreceptors within the follicle.