Pain Sensitivity In Humans Research Articles

Receptors and channels: Association between haplotype structure in the genes encoding thermosensitive channels and experimental pain sensitivity in European Americans

The objective was to consider the low to moderate heritability estimates of pain sensitivity and large number of related genes, a haplotype map may provide a better tool in investigating the role of genetic factors in pain than single individual polymorphisms. We generated haplotype blocks based on the single nucleotide polymorphisms (SNPs) from δ opioid receptor subtype 1 gene (OPRD1), transient receptor potential V subtype1 gene (TRPV1), transient receptor potential M subtype 8 gene (TRPM8) and ankyrin-like with transmembrane domains 1 gene (ANKTM1). We investigated the association between these haplotype blocks and experimental thermal and cold pain sensitivity in European American population. European American subjects (N=310) provided ratings of sensory intensity for heat stimuli applied to the volar forearm and for a 3 min cold pressor test using a standard 10 cm visual analog scale. For genotyping of genomic DNA, 5' exonuclease allelic discrimination assays were performed. Haplotype frequency of unphased genotypes was inferred using PHASE method and measured linkage disequilibrium by Lewontin's Disequilibrium coefficient, D prime. We identified haplotype blocks, which shows little evidence of recombination OPRD1, TRPV1, TRPM8 and ANKTM1. All the genotypes assessed with GeneStat program assume Hardy-Weinberg Equilibrium. We found a significant relationship between 2 haplotype blocks in ANKTM1 and the cold pain sensitivity in European American population. These data suggest the role of genetic factors based on haplotype blocks in experimental pain sensitivity in humans and support the role of ANKTM1 in the perception of experimental cold pain.

Psychophysics/hyperalgesia: The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans

Responses to painful stimuli are characterized by tremendous inter-individual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) was associated with responses to three different experimental pain modalities in a sample of 157 healthy volunteers (88 female, 69 male). The following psychophysical pain measures were obtained in all subjects: heat pain threshold and tolerance, temporal summation of thermal pain, pressure pain threshold at three sites (trapezius, ulna, and masseter), and ischemic pain threshold and tolerance. Using DNA extracted from whole blood, a 302 base pair fragment of the OPRM1 gene was PCR amplified and sequenced using PCR primers. Genotyping of OPRM1 revealed that the rarer allele at A118G occurred in 20 females (22%) and 11 males (16%). Statistical analyses indicated no significant genotype group differences in thermal or ischemic pain responses; however, subjects with the rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. While no interaction with sex emerged, the effect sizes (Cohen's D) for the genotype difference ranged from .46 to .84 for males and ..13 to .42 for females, suggesting a stronger association among males. Independent of genotype, sex differences also emerged for heat pain tolerance and pressure pain threshold. These data indicate an association of a common SNP of OPRM1 with mechanical pain responses, especially among men, providing the first evidence in humans that this previously identified candidate gene may indeed be association with pain sensitivity. Potential mechanisms underlying these results are discussed.

Human head exposure to a 37 Hz electromagnetic field: effects on blood pressure, somatosensory perception, and related parameters.

Previous studies have shown that exposure to an electromagnetic field (EMF) of 37 Hz at a flux density of 80 microT peak enhances nociceptive sensitivity in mice. Here we examined the effects on pain sensitivity and some indexes of cardiovascular regulation mechanisms in humans by measuring electrical cutaneous thresholds, arterial blood pressure, heart rate and its variability, and stress hormones. Pain and tolerance thresholds remained unchanged after sham exposure but significantly decreased after electromagnetic exposure. Systolic blood pressure was significantly higher during electromagnetic exposure and heart rate significantly decreased, both during sham and electromagnetic exposure, while the high frequency (150-400 mHz) component of heart rate variability, which is an index of parasympathetic activity, increased as expected during sham exposure but remained unchanged during electromagnetic exposure. Cortisol significantly decreased during sham exposure only. These results show that exposure to an EMF of 37 Hz also alters pain sensitivity in humans and suggest that these effects may be associated with abnormalities in cardiovascular regulation.

Evaluation of single nucleotide polymorphisms in genes related to the vanilloid receptor and cyclooxygenase‐2 in human pain sensitivity

Clinical Pharmacology & Therapeutics (2003) 73, P98–P98; doi:

Behavioral measurement of thermal pain sensitivity in humans: Effects of stimulus intensity and instructions.

Behavioral measurement of thermal pain sensitivity in humans: Effects of stimulus intensity and instructions.

Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects

Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = −0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 ± 1 vs. +9 ± 1 mmHg NT vs. BH group), CVP (+0.7 ± 0.1 vs. +0.5 ± 0.1 mmHg), HR (+2 ± 1 vs. +2 ± 1 beats/min), and MSNA (+5 ± 1 vs. +4 ± 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.

Do endogenous opioids mediate the relationship between blood pressure and pain sensitivity in normotensives?

Elevated resting blood pressure is associated with decreased pain sensitivity in both animals and humans. Recent evidence suggests that this relationship may be mediated by endogenous opioid peptides in hypertensives, but the precise mechanism has not been investigated in normotensives. We examined the effect of opioid receptor blockade with naloxone on the relationship between resting blood pressure and pain sensitivity in normotensive humans. Sixteen young adults were given cold pressor and handgrip challenges after treatment with either naloxone or saline in a placebo-controlled, within-subject design. Multiple regression procedures indicated that resting systolic blood pressure was a significant predictor of cold pain ratings even after the effects of naloxone were statistically controlled. The interaction between systolic blood pressure and opioid blockade was non-significant. These data suggest that the relationship between resting blood pressure and pain sensitivity in normotensive humans is mediated, at least in part, by non-opioid mechanisms.

A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated

The effect of breathing CO2 on somatic sensitivity was studied in human subjects. Healthy humans breathed room air, 100% O2, or CO2 (5% or 8% in O2). Thresholds to heat pain, mechanical pain, electrically evoked pain, and electrically evoked perception were measured using psychophysical techniques. Also, the effects on sensory and affective components of experimental ischaemic pain, alertness and on cardiovascular parameters were observed. In addition, the effect of CO2 on heat pain threshold was determined in the ischaemic limb to exclude the possibility that the threshold elevation was due to an action on primary afferent fibres. Naloxone (0.8 mg), dexamethasone (0.1 mg) or placebo (0.9% NaCl) were applied intravenously in double blind tests to reverse the threshold elevations. In an electrophysiological experiment the effect of CO2 on a spinal nociceptive flexion reflex evoked by an electric stimulus was measured. The CO2 produced a dose-dependent elevation of the heat pain threshold. Similarly, the sensory and affective components of experimental ischaemic pain were attenuated by CO2. The heat pain threshold was significantly elevated by CO2 in the ischaemic limb, also. However, there was no effect on thresholds to mechanically or electrically induced pain or perception thresholds to electrically evoked sensations. One hundred percent O, did not elevate the heat pain threshold. In double blind tests the heat pain threshold elevation was not significant when the naloxone or dexamethasone was administered. The threshold to electrically evoked spinal flexion reflex was not elevated by CO2. The CO2 at the current dose produced sedation, an increase in blood pressure but no change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered Pain and Visual Sensitivity in Humans: The Effects of Acute and Chronic Stressa

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Mood, performance, and pain sensitivity: Changes induced by food constituents

We examined the behavioral effects of the dietary constituents tryptophan and tyrosine on human mood, sensorimotor performance and pain sensitivity. Tryptophan and tyrosine are neurotransmitter precursors present in varying amount in protein-containing foods. Tryptophan (50 mg/kg) increased subjective drowsiness and fatigue but unlike many hypnotics did not impair sensorimotor performance. Tryptophan also decreased human pain sensitivity in a manner that was more specific than certain analgesic drugs.