ABSTRACT
UNLABELLED: Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain. PERSPECTIVE: The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia.
Subject(s)
Gap Junctions/physiology , Pain/physiopathology , Posterior Horn Cells/physiology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Ulcer Agents/pharmacology , Carbenoxolone/pharmacology , Chronic Disease , Gap Junctions/drug effects , Glycyrrhizic Acid/pharmacology , HIV Envelope Protein gp120/pharmacology , Hyperalgesia/physiopathology , Injections, Spinal , Interleukin-1/metabolism , Male , Nerve Compression Syndromes/physiopathology , Rats , Rats, Sprague-Dawley , Sciatic Neuropathy/physiopathology , Specific Pathogen-Free OrganismsABSTRACT
Previous studies have found inconsistent relationships between restrained eating, dieting, and cortisol. The present study was designed to clarify the relationship between self-reported restrained eating and cortisol using multiple measures of dietary restraint. Eighty-five college-age women completed the Restraint Scale (RS) and the Cognitive Restraint Scale of the Three Factor Eating Questionnaire (TFEQ-R) and provided a saliva sample for analysis of cortisol. Both measures of restraint were positively associated with elevated levels of salivary cortisol, although the TFEQ-R was more strongly associated than the RS. Restrained eating, characterized by largely unsuccessful efforts to control eating, may lead to elevated cortisol levels.
