Patients with acute
herpes zoster, and to a lesser extent post-herpetic
neuralgia (PHN), have been reported to respond to
local anesthetic blockade of the sympathetic nervous system. In animal models of nerve injury, local injection of
adrenergic agonists after nerve injury, but not before, excites nociceptors. In some patients with chronic
neuropathic pain, local application of
norepinephrine evokes
pain. In 15 subjects with PHN, the role of
adrenergic receptors in PHN
pain was assessed in a two-session double blind study comparing the response to cutaneous infiltration of
epinephrine or
phenylephrine (30 micrograms in 3 ml) with the response to
normal saline in both the painfully affected skin and mirror-image normal skin. Two adjacent sites were studied on each side of the body, one site for injection and the other for measuring sensory effects of the injection. In the morning part of each session, mirror-image normal skin was injected. In the afternoon portion of each session, skin in the most painful area affected by PHN was injected. Injection of saline or the
adrenergic agonist in normal skin produced mild and transient
pain without development of
allodynia and without affecting overall PHN
pain intensity. In PHN skin, injection of saline and the
adrenergic agonist produced an equivalent degree of transient
pain that was slightly greater than injection into mirror-image normal skin. After injection of the
adrenergic agonist into PHN skin, both overall PHN
pain and
allodynia severity were significantly greater than after saline injection, peaking
at 10-15 min post-injection. Even when PHN has been present for years,
adrenergic receptor stimulation in PHN skin increases
pain, most likely through direct activation of C-nociceptors in the painful skin. Increased
allodynia is most likely mediated centrally and driven by the increase in C-nociceptor input.