The role of nociceptors of cutaneous veins in the mediation of cold pain in man.

1. To test the hypothesis that nociceptors of cutaneous veins mediate cold pain, we studied in man the time course of pain intensity and skin sensibility in relation to both intracutaneous and vein wall temperature during cooling of the dorsum of the hand by ice water before and after perivenous and intravenous nerve block. 2. Upon exposure to cold, intracutaneous temperatures fell exponentially (half-life/45-75s) within 10 min to a median of 4 degrees C (range 2-9 degrees C) and returned to baseline with a similar time course during rewarming (half-life/40-85 s). 3. Skin sensitivity to pin prick disappeared and returned at almost the same intracutaneous temperatures (16-26 degrees C). Pain, however, occurred and eve increased when the skin was already numb. 4. Pain occurred during cooling and disappeared during rewarming at vein wall temperatures between 23 and 28 degrees C and its intensity increased to a maximum of 72-100% of visual analogue scale as vein wall temperature decreased to a minimum of 9 degrees C (range 7-10.5 degrees C). 5. the pain intensity-vein wall temperature relations derived from skin cooling with threshold temperature changes between -5.5 and -9 degrees C and slopes between 2.2 and 3.3 were congruent to those derived from intravenous cooling in a previous study to ours. 6. Perivenous and intravenous nerve block, which did not alter the sensitivity of skin and periosteum, relieved cold pain markedly (perivenous block) or completely (intravenous block). 7. These observations are consistent with the hypothesis that nociceptors of cutaneous veins mediate cold pain in humans.