Brain, behavior, and immunity
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Brain Behav. Immun. · Jul 2007
Satellite glial cells in sensory ganglia: their possible contribution to inflammatory pain.
Neurons in dorsal root ganglia (DRG) are surrounded by an envelope of satellite glial cells (SGCs). Little is known about SGC physiology and their interactions with neurons. In this work, we investigated changes in mouse DRG neurons and SGC following the induction of inflammation in the hind paw by the injection of complete Freund's adjuvant (CFA). ⋯ Intraperitoneal injection of the gap junction blocker carbenoxolone prevented the inflammation-induced decrease in pain threshold. The results show that augmented glial coupling is one of the major events occurring in DRG following inflammation. The elevation in pain threshold after carbenoxolone administration provides indirect support for the idea that augmented intercellular coupling might contribute to chronic pain.
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Brain Behav. Immun. · Feb 2007
Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury.
Increasing evidence points to a role for spinal neuroimmune dysregulation (glial cell activation and cytokine expression) in the pathogenesis of chronic pain. Suppression of astrocytic and microglial activation with the methylxanthine derivative, propentofylline, pre-emptively attenuates the development of nerve injury-induced allodynia. Currently, we investigated the ability of systemic propentofylline to reverse existing, long-term allodynia after nerve injury--a clinically relevant paradigm. ⋯ Less robust increases in GFAP immunoreactivity were observed at days 28 and 42 post-transection. Interestingly, propentofylline treatment suppressed microglial activation at both time points in this paradigm. Taken together, our results highlight the clinical potential of the glial modulating agent, propentofylline, for the treatment of neuropathic pain as well as a role for microglia in the long-term maintenance of allodynia.
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Brain Behav. Immun. · Feb 2007
Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids.
Within the past decade, there has been increasing recognition that glia are far more than simply "housekeepers" for neurons. This review explores two recently recognized roles of glia (microglia and astrocytes) in: (a) creating and maintaining enhanced pain states such as neuropathic pain, and (b) compromising the efficacy of morphine and other opioids for pain control. While glia have little-to-no role in pain under basal conditions, pain is amplified when glia become activated, inducing the release of proinflammatory products, especially proinflammatory cytokines. ⋯ Products of activated glia increase neuronal excitability via numerous mechanisms, including direct receptor-mediated actions, upregulation of excitatory amino acid receptor function, downregulation of GABA receptor function, and so on. These downstream effects of glial activation amplify pain, suppress acute opioid analgesia, contribute to the apparent loss of opioid analgesia upon repeated opioid administration (tolerance), and contribute to the development of opioid dependence. The potential implications of such glial regulation of pain and opioid actions are vast, suggestive that targeting glia and their proinflammatory products may provide a novel and effective therapy for controlling clinical pain syndromes and increasing the clinical utility of analgesic drugs.
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Brain Behav. Immun. · Jan 2007
Comparative StudyEffects of carrageenan and morphine on acute inflammation and pain in Lewis and Fischer rats.
The present study used inbred, histocompatible Fischer 344 (FIS) and Lewis (LEW) rats to begin to explore the role of the hypothalamic-pituitary-adrenal (HPA) axis in the immune processes and pain behavior associated with the carrageenan model of acute hindpaw inflammation. Because the HPA axis contributes in part to morphine's analgesic and immunomodulatory properties, the present study also assessed the effects of morphine in carrageenan-inflamed LEW and FIS rats. The results showed that carrageenan-induced hindpaw swelling and pain behavior were greater in FIS than in LEW rats. ⋯ In fact, low doses of morphine produced a mechanical allodynia and hyperalgesia in the noninflamed hindpaw of FIS, but not LEW, rats. These results suggest a positive relationship between HPA axis activity and acute inflammation and inflammatory pain. In contrast, little evidence is provided for HPA axis involvement in morphine's anti-inflammatory or analgesic effects.
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Brain Behav. Immun. · Sep 2006
ReviewExpectations and associations that heal: Immunomodulatory placebo effects and its neurobiology.
The use of placebo may have accompanied healing and medical practices since their origins (Plato; Charmides, 155-156). Recent experimental data indicate that we would be well advised to further consider placebo effects in future therapeutic strategies, with a better knowledge of their potency, psychological basis and underlying neurobiological mechanisms. Current research in the areas of pain, depression and Parkinson's disease has uncovered some of the potential neurobiological mechanisms of placebo effects. ⋯ To date, research on placebo responses affecting immune-related diseases is scarce, but there are consistent indications that skin and mucosal inflammatory diseases, in particular, are strongly modulated by placebo treatments. However, the brain's capability to modulate peripheral immune reactivity has been impressively demonstrated by paradigms of behavioral conditioning in animal experiments and human studies. Thus, placebo effects can benefit end organ functioning and the overall health of the individual through positive expectations and behavioral conditioning processes.