TY - JOUR T1 - Carriers of Recessive <em>WNK1</em>/<em>HSN2</em> Mutations for Hereditary Sensory and Autonomic Neuropathy Type 2 (HSAN2) Are More Sensitive to Thermal Stimuli JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2162 LP - 2166 DO - 10.1523/JNEUROSCI.4633-08.2009 VL - 29 IS - 7 AU - Marco L. Loggia AU - M. Catherine Bushnell AU - Martine Tétreault AU - Isabelle Thiffault AU - Claude Bhérer AU - Nazma K. Mohammed AU - Anil A. Kuchinad AU - Audrey Laferrière AU - Marie-Josée Dicaire AU - Lina Loisel AU - Jeffrey S. Mogil AU - Bernard Brais Y1 - 2009/02/18 UR - http://www.jneurosci.org/content/29/7/2162.abstract N2 - Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in the HSN2 gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p &lt; 0.001) and cool (p &lt; 0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p = 0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p &lt; 0.01) and cold pain stimuli (p &lt; 0.05), and tend to be more sensitive to cool stimuli (p = 0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r = 0.76, p = 0.02), and in carriers cool detection thresholds did not increase with age (r = 0.27, p = 0.24) as expected and observed in controls (r = 0.34, p = 0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state. ER -