Biomedical subjects

Gustavo Pacheco-López

Publications and source records attributed to Gustavo Pacheco-López.

6 recordsLinked to original sources

PubMed2006

Expectations 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. These data indicate that conscious expectation and unconscious behavioral conditioning processes appear to be the major neurobiological mechanisms capable of releasing endogenous neurotransmitters and/or neurohormones that mimic the expected or conditioned pharmacological 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.

Brain↗

PubMed2006

Murine taste-immune associative learning.

Taste-immune associative learning can result from contingent pairings of an immune-competent unconditioned stimulus (US) with a gustative conditioned stimulus (CS). Recalling such an association may induce a set of physiological responses affecting behavior, endocrine, and immune functions. We have established a model of behaviorally conditioned immunosuppression employing the immunosuppressant drug cyclosporine A (CsA) as the US and saccharin as the CS in rats and humans. In order to investigate the inter-species generalization of this neuro-immune interaction, we tested the feasibility of this paradigm in mice. In a single-bottle scheme, male BALB/c mice (n=5) were conditioned by conducting three association trials and a single recall trial. Control groups (n=5/group) were designed to assure associative learning, pharmacological effects of the US, and placebo effect. Results show that CsA-conditioned animals displayed significant immunosuppression in the spleen after recall, measured by in vitro T-lymphocyte proliferation, and IL-2 production. However, the same animals did not show evidence of avoidance behavior to the CS. In contrast, evoking the association of saccharin-lithium chloride (inducing gastric malaise) in another set of animals (n=4/group) resulted in significant and pronounced avoidance of the taste (CS). These animals also displayed significant suppression of splenic T-lymphocyte responsiveness after the recall phase. The present results indicate that mice seem to be capable of associating a gustative stimulus with CsA, resulting in behaviorally conditioned immunosuppression without affecting appetitive behavior.

Analysis of Variance↗

PubMed2005

Neural substrates for behaviorally conditioned immunosuppression in the rat.

We have previously demonstrated behaviorally conditioned immunosuppression using cyclosporin A as an unconditioned stimulus and saccharin as a conditioned stimulus. In the current study, we examined the central processing of this phenomenon generating excitotoxic lesions before and after acquisition to discriminate between learning and memory processes. Three different brain areas were analyzed: insular cortex (IC), amygdala (Am), and ventromedial nucleus of the hypothalamus (VMH). The results demonstrate that IC lesions performed before and after acquisition disrupted the behavioral component of the conditioned response (taste aversion). In contrast, Am and VMH lesions did not affect conditioned taste aversion. The behaviorally conditioned suppression of splenocyte proliferation and cytokine production (interleukin-2 and interferon-gamma) was differentially affected by the excitotoxic lesions, showing that the IC is essential to acquire and evoke this conditioned response of the immune system. In contrast, the Am seems to mediate the input of visceral information necessary at the acquisition time, whereas the VMH appears to participate within the output pathway to the immune system necessary to evoke the behavioral conditioned immune response. The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.

Amygdala↗

PubMed2004

Repeated acupuncture treatment affects leukocyte circulation in healthy young male subjects: a randomized single-blind two-period crossover study.

Acupuncture is the most popular component of traditional Chinese medicine in western countries, which has been widely used in the treatment of numerous medical conditions, e.g., pain, emesis or asthma. However, the effects of acupuncture on neuroendocrine and immune functions in humans remain unclear. Therefore, the present study was performed to analyse whether acupuncture treatment affects leukocyte circulation as well as plasma levels of cortisol and norepinephrine in humans. Ten healthy young male subjects were enrolled in a randomized single-blind two-period crossover study. Each period contained three sessions of either acupuncture or sham acupuncture (placebo) treatment. After randomisation, the group 1 (n=5) received acupuncture treatment at acu-points ST36, LI11, SP10, and GV14, while sham acupuncture was performed for group 2 (n=5). Two weeks later, each group received the alternative treatment. Blood samples were taken before needling, 10 min after, and 30 min after removing the needles in the first and the third session. In addition, blood pressure and heart rate were determined simultaneously. Although acupuncture treatment did not affect leukocyte circulation in peripheral blood after the first session, we observed a significant decrease in leukocyte and lymphocyte values after the third session. In contrast, cortisol and norepinephrine plasma levels remained unchanged by acupuncture. These data indicate that repeated acupuncture treatment can affect leukocyte circulation in healthy humans by still unknown mechanisms.

Acupuncture Therapy↗

PubMed2003

Central catecholamine depletion inhibits peripheral lymphocyte responsiveness in spleen and blood.

Experimental and clinical evidence has demonstrated extensive communication between the CNS and the immune system. To analyse the role of central catecholamines in modulating peripheral immune functions, we injected the neurotoxin 6-hydroxydopamine (6-OHDA) i.c.v. in rats. This treatment significantly reduced brain catecholamine content 2, 4 and 7 days after injection, and in the periphery splenic catecholamine levels were reduced 4 days after treatment. Central catecholamine depletion induced an inhibition of splenic and blood lymphocyte proliferation and splenic cytokine production and expression (interleukin-2 and interferon-gamma) 7 days after injection. In addition, central treatment with 6-OHDA reduced the percentage of spleen and peripheral blood natural killer (CD161 +) cells, and T-cytotoxic (CD8 +) cells in peripheral blood. The reduction in splenocyte proliferation was not associated with a glucocorticoid alteration but was completely abolished by prior peripheral sympathectomy. These data demonstrate a crucial role of central and peripheral catecholamines in modulating immune function.

Animals↗

PubMed2002

Peripheral protein immunization induces rapid activation of the CNS, as measured by c-Fos expression.

To investigate immune-to-brain communication, we challenged rats intraperitoneally with a protein antigen (keyhole limpet hemocyanin, KLH), and measured c-Fos expression in different brain structures. We found a rapid c-Fos expression 120 min after immunization in brain stem and forebrain structures, using a dose of KLH not inducing fever or malaise. Using proper controls, we found that this central response is related to the immunogenicity of the antigen and the magnitude of the immune response. Our results suggest that different interconnected brain cell groups respond rapidly to an immune challenge in the periphery, constituting an afferent pathway of neuroimmune communication.

Animals↗