[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 267.15/FF21
Topic: D.08.j. Pain models
Support: NINDS grants NS 14627
NS 47113
NS 48499
Title: A behavioral model of episodic cranial pain in mice conditions a place aversion
Authors: *A. H. AHN 1 , E. MARTIN 2 , A. I. BASBAUM 3 ;
1 Neurol, 2 Anat., 3 Anatomy, Physiol. and WM Keck Ctr. for Integrative Neurosci., Univ.
California San Francisco, San Francisco, CA
Abstract: We have adapted a widely-used behavioral model of inflammation and tissue-injury
pain, the formalin test of the hindpaw, to model behaviors associated with episodic cranial pain.
In wild-type CD1 male mice, a midline intradermal injection of 10 microliters of dilute formalin,
overlying the coronal suture (Bregma), produces stereotypical, localized grooming behaviors that
develop in intensity over 10-20 min and resolve by approximately 45 min after injection. The
time the animals spend in this directed grooming behavior is largely non-existent in animals
injected with saline, but is prominent and dose-dependent, in a range of formalin concentrations
from 0.5 to 3.0 %. Unlike the traditional formalin test of the hindpaw, or even formalin injection
of the lip or vibrissal pad, the cranial formalin test does not show a clear pause in the nociceptive
behaviors after the first 5 min after injection. With 2.0% formalin used for subsequent tests, the
behaviors are not reduced by the pre-treatment of 5.0 mg/kg morphine, but are reduced by 10.0
mg/kg morphine. Two hours after the injection of formalin, the stimulus elicits Fos expression, a
cellular marker of neuronal activation, in the dorsal horn of the upper cervical spinal cord and
trigeminal nucleus caudalis, as well as in the external parabrachial nuclei. Another marker of
cellular activation, phosphorylated extracellular signal-related kinase (pERK) is induced in the
central nucleus of the amygdala, suggesting that this stimulus is aversive.
To functionally test whether this stimulus is a behaviorally aversive signal, we used a
Conditioned Place Aversion (CPA) paradigm. We conditioned 12-14 mice with daily sessions of
2% formalin injection in one room, paired with saline on alternate days. We used a balanced
CPA design in which half of the animals were conditioned in each room of a two-chamber
system, with half of the animals receiving formalin on the first day, and half with saline. Cranial
formalin produced a dose-dependent aversion for the formalin-paired room. Furthermore, low
doses of morphine, at 5.0 mg/kg, were sufficient to completely block CPA, suggesting that the
aversive association can be blocked independently of the expression of nociceptive behavior.
Disclosures: A.H. Ahn , None; A.I. Basbaum, None; E. Martin, None.