On the premises of clinical studies, a possible contribution of oxygen
radicals has been considered to the development of inflammatory pain
and hyperalgesia. In a rat skin-saphenous nerve preparation using stan
dard teased-fiber techniques (n = 57) hydrogen peroxide (1 mM, 10 mM a
nd 50 mM) was applied in aqueous solution to cutaneous nerve endings o
f unmyelinated nociceptive afferents. Superoxide anion and hydroxyl ra
dical were secondarily generated as reaction products from pyrogallol
(1 and 10 mM) and from Fe-EDTA (1 mM) in hydrogen peroxide, respective
ly. None of these substances, except exceptionally, induced ongoing ac
tivity nor nociceptor sensitization to heat and mechanical stimuli. If
occasionally there was a weak excitatory effect, the fibers were left
with a profound desensitization to adequate stimulation. The addition
of hydrogen peroxide did not enhance sustained responses to solutions
of high proton concentration (pH 6.1). Responses to combined inflamma
tory mediators (bradykinin, serotonin, histamine and prostaglandin E(2
), 10 mu M) were increased, on average, when hydrogen peroxide was add
ed but this effect did just not reach significance. These findings sug
gest that oxygen radicals do not play a major and specific role in noc
iceptor sensitization.