Perceived intensity and unpleasantness of cutaneous and auditory stimuli: an evaluation of the generalized hypervigilance hypothesis.

According to the Generalized Hypervigilance Hypothesis (GHH) of McDermid et al., the unpleasantness of sensory stimuli, rather than their modality, determines whether they will be perceptually amplified in hypervigilant persons. In a test of this idea, ratings of the intensity of sensations evoked by cutaneous and auditory stimuli were obtained from individuals with chronic myofascial pain (fibromyalgia, temporomandibular disorders), and from (less hypervigilant) healthy control participants. In each modality, the stimuli spanned a wide intensity range, with the weakest stimuli being affectively neutral and the strongest being distinctly unpleasant, as determined by unpleasantness ratings. The pain patients showed robust perceptual amplification of the cutaneous pressure stimuli, and modest amplification of the auditory stimuli. In both cases, perceptual amplification extended to even the lowest stimulus intensities, a result that is not consistent with the predictions of the GHH. An alternative formulation, the attentional gain control model of hypervigilance, is proposed, according to which those types of stimuli that are associated with pain are amplified because of the attention that is habitually directed toward them.

Dominance of high-producing interleukin 6 and low-producing interleukin 10 and interferon gamma alleles in glucose-6-phosphate dehydrogenase-deficient trauma patients.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a condition associated with malaria resistance, is a common genetic polymorphism. Decreased interleukin (IL)-10 production was demonstrated in vivo and in vitro in the African and Mediterranean forms of G6PD deficiencies. We hypothesized that low-producing IL-10 alleles are more abundant in the G6PD-deficient than nondeficient population. One hundred eleven men with African American ancestry were tested for G6PD deficiency (Type A-202/376) and for the cytokine gene promoter polymorphisms of IL-10 (-1082 G/A, -819 T/C, and -592 A/C), tumor necrosis factor (TNF)-alpha (-308 G/A), transforming growth factor (TGF)-beta1 (C/T codon 10 and C/G codon 25), IL-6 (-174 G/C), and interferon (IFN)-gamma (+874 A/T). There were no differences in the allele frequencies for TNF-alpha, IL-6, or TGF-beta1 between the G6PD-deficient and nondeficient population. In contrast, the low-producing IL-10 alleles (-592A) and low-producing IFN-gamma (+874A) allele frequencies were greater in G6PD-deficient than nondeficient samples (P = 0.035 and 0.009). Seventy-one percent of G6PD-deficient and 50% of nondeficient samples carried the high-producing IL-6(G) allele with low-producing IL-10(A) allele (P = 0.03). Furthermore, 95% of deficient and 81% of nondeficient samples carried the IL-6(G) allele together with low-producing IFN-gamma(A) allele (P = 0.017). These investigations indicate a predominant presence of high-producing IL-6 alleles together with low-producing IL-10 and IFN-gamma alleles in individuals with ancestry from malaria-endemic regions. The frequency of low-producing IL-10 genotypes is greater in the G6PD-deficient compared with nondeficient patients. The fact that these genetic differences are preserved in the current African American G6PD-deficient population indicates their potential role in pathophysiological processes in the absence of the selective pressure caused by tropical diseases.

Attenuated monocyte IL-10 production in glucose-6-phosphate dehydrogenase-deficient trauma patients.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the world's most common known human genetic polymorphisms, but the pathophysiology of the defect remains largely unknown. In the present study, we compared hematology parameters and ex vivo monocyte cytokine responses in non-deficient and G6PD-deficient trauma patients. Deficient and non-deficient, moderately injured, trauma patients exhibited similar hematology profiles at the time of hospital admission. In contrast to non-deficient patients, G6PD-deficient patients were anemic 2 days post-injury. Monocytes from deficient individuals produced 50% less interleukin 10 (IL-10) in response to LPS and >90% less IL-10 in response to PMA, compared with non-deficient patients, 2 days post-injury. The presence of phenylhydrazine-treated, opsonized, autologous RBC (OX-RBC), alone had no effect on IL-10 production by non-deficient or deficient monocytes, whereas IL-10 responses to lipopolysaccharide (LPS) were augmented by OX-RBC in both groups. However, IL-10 production was markedly lower by monocytes from G6PD-deficient than non-deficient patients after stimulation with LPS plus OX-RBC. TNF-alpha production following PMA was similar in deficient and non-deficient patients, and the differences following LPS or LPS plus OX-RBC stimulation were moderate between deficient and non-deficient samples. Interferon (IFN)-gamma production ex vivo was doubled by OX-RBC treatment alone, but it was not stimulated by LPS treatment. IFN-gamma production was similar in non-deficient and G6PD-deficient patients. These data suggest that the observed differences in IL-10 responses between G6PD-deficient and non-deficient patients are not attributable to differences in TNF-alpha or IFN-gamma production. Taken together, our data suggest that a reduction in the capacity to produce IL-10 may be an intrinsic characteristic of G6PD-deficient monocytes. An attenuated IL-10 production may be a contributing mechanism in the previously observed augmented inflammatory response in severely injured G6PD-deficient compared with non-deficient trauma patients.