Clonidine is approved for spinal administration against
neuropathic pain, and reverses both spontaneous and elicited
pain in humans following spinal administration. Rodent studies that seek to model pharmacology in
pain states have historically relied on reflexive withdrawal from noxious stimuli as the primary endpoint. Drug
self-administration studies have face validity in the
drug abuse field for modeling
drug abuse in humans, however, this methodology has not been applied to address issues related to drug seeking behaviors that may be relevant for other human populations, such as patients with
neuropathic pain. Rats without spinal nerve
ligation (SNL) failed to acquire intrathecal
clonidine self-administration over 10 days of access. Rats were found to self-administer intrathecal infusions of
clonidine following SNL in a stable and dose-responsive manner, however, and
clonidine was self-administered throughout the day with 66% of total drug intake occurring during the dark cycle. Substitution of
clonidine with saline or with
clonidine and the alpha2-adrenoceptor antagonist
idazoxan resulted in extinction of responding in SNL animals. Food reinforcement was initially decreased in SNL rats self-administering
clonidine compared to normal animals, however, tolerance developed to this effect of
clonidine in SNL rats after 5 days. These data demonstrate that drug
self-administration can be applied to questions other than
drug abuse, and provides an additional measure for development of novel therapeutic strategies for
chronic pain treatment.