The Journal of Neuroscience, July 1, 2002, 22(13):5687-5693
Stimulation of Deep Somatic Tissue with Capsaicin Produces
Long-Lasting Mechanical Allodynia and Heat Hypoalgesia that Depends on
Early Activation of the cAMP Pathway
K. A.
Sluka
Graduate Program in Physical Therapy and Rehabilitation Science,
Neuroscience Graduate Program, Pain Research Program, University of
Iowa, Iowa City, Iowa 52242
Pain and hyperalgesia from deep somatic tissue (i.e., muscle and
joint) are processed differently from that from skin. This study
examined differences between deep and cutaneous tissue allodynia and
the role of cAMP in associated behavioral changes. Capsaicin was
injected into the plantar aspect of the skin, plantar muscles of the
paw, or ankle joint, and responses to mechanical and heat stimuli were
assessed until allodynia resolved. Capsaicin injected into skin
resulted in a secondary mechanical allodynia and heat hypoalgesia
lasting ~3 hr. In contrast, capsaicin injection into muscle or joint
resulted in a long-lasting bilateral (1-4 weeks) mechanical allodynia
with a simultaneous unilateral heat hypoalgesia. The pattern and degree
of inflammation were similar when capsaicin was injected into skin,
muscle, or joint, with peak increases 24 hr after injection. Heat
hypoalgesia that occurs after injection into deep tissue was reversed
by spinal blockade of adenylate cyclase or protein kinase A (PKA).
Interestingly, mechanical allodynia was reversed if adenylate cyclase
or PKA inhibitors were administered spinally 24 hr, but not 1 week,
after injection of capsaicin. Spinally administered 8-bromo-cAMP
resulted in a similar pattern, with heat hypoalgesia and mechanical
allodynia occurring simultaneously. Thus, injection of capsaicin into
deep tissues results in a longer-lasting mechanical allodynia and heat
hypoalgesia compared with injection of capsaicin into skin. The
mechanical allodynia depends on early activation of the cAMP pathway
during the first 24 hr but is independent of the cAMP pathway by 1 week
after injection of capsaicin.
Key words:
pain; analgesia; protein kinase A; adenylate cyclase; muscle; joint
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135687-07$05.00/0
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