European journal of pain : EJP
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The fundamental aspects of bone associated pain in humans are not fully understood. In this study pressure pain applied to the tibia bone was investigated experimentally in humans and by means of computer simulations. In humans, the pressure pain sensitivity and the relation between tissue indentation and pressure intensity were recorded by a computer-controlled pressure algometer with two different probe sizes (0.03 cm(2) and 1.0 cm(2)). ⋯ For both probes the strain peaked in adipose tissue at 0.29, and in the bone interface it was reduced by 3% (0.03 cm(2)) and 15% (1.0 cm(2)), respectively. For both probes the stress peaked at 235 kPa in skin layer, and in the deeper layers it was reduced to 50 kPa. Mechanosensitive nociceptors innervating the periosteum are ideally placed to mediate pain evoked by pressure stimulation on the tibia bone and small diameter probes may be optimal for assessing bone associated pain sensitivity.
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Chronic neuropathic pain arising from peripheral nerve damage is a severe clinical issue where there is a major unmet medical need. We previously demonstrated that both neurotensin (NT) receptor subtypes 1 (NTS1) and 2 (NTS2) are involved in mediating the naloxone-insensitive antinociceptive effects of neurotensin in different analgesic tests including hotplate, tail-flick, and tonic pain. However, the role of these receptors in neuropathic pain management has been poorly investigated. ⋯ Intrathecal administration of the NTS1-selective agonist, PD149163 (30-90 μg/kg) also produced potent anti-allodynic and anti-hyperalgesic effects in nerve-injured rats. Likewise, heat hyperalgesia and tactile allodynia produced by CCI of the sciatic nerve were fully reversed by the NTS1 agonist, NT69L (5-25 μg/kg). Altogether, these results support the idea that the NTS1 receptor subtype is involved in pain modulation, and the potential use of NTS1 agonists for the treatment of painful neuropathies.
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Sleep of good quantity and quality is considered a biologically important resource necessary to maintain homeostasis of pain-regulatory processes. To assess the role of chronic sleep disturbances in pain processing, we conducted laboratory pain testing in subjects with primary insomnia. Seventeen participants with primary insomnia (mean ± SEM 22.6 ± 0.9 yrs, 11 women) were individually matched with 17 healthy participants. ⋯ Pain inhibition, as assessed with the diffuse noxious inhibitory control paradigm (DNIC), was attenuated in insomnia subjects when compared to controls (p < 0.05). Based on these findings, we propose that pain-inhibitory circuits in patients with insomnia are in a state of constant activation to compensate for ongoing subclinical pain. This constant activation ultimately may result in a ceiling effect of pain-inhibitory efforts, as indicated by the inability of the system to adequately function during challenge.
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Electrical low-frequency stimulation induces central neuroplastic changes of pain processing in man.
Electrical low-frequency stimulation (LFS) inhibits pain perception and nociceptive processing as shown by psychophysical and electrophysiological means (long-term depression, LTD). Information regarding central mechanisms involved in LTD induction and maintenance are still missing. This study hypothesizes that electrical LFS induces changes in activation pattern of pain-related brain areas. ⋯ P2 dipole location analysis yielded a significant posterior (p < 0.05) shift following LTD induction. Thus, data reveal central changes of pain processing after LTD induction. These experiments may help judging the potency of LTD as model for electrostimulation in future analgesic therapy.
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Visceral hyperalgesia is a multifactorial gastrointestinal disorder which featured with alterations of abdominal motility and/or gut sensitivity, and is believed to be triggered by environmental stressor or psychological factors. However, its etiology remains incompletely understood. In this study, we aimed to investigate whether nerve growth factor (NGF)-mediated neuronal plasticity is involved in neonatal maternal separation (NMS)-induced visceral hypersensitivity in adult rats, and whether NGF antagonist can attenuate or block such development. ⋯ Further, as intra-peritoneal administration of NGF (10 μl at 1 μg/kg/day) was given to NH rats during neonatal period, effects that comparable to NMS induction were observed in the adulthood. In contrast, when NMS rats were treated with NGF antagonist K252a (10 μl/day from postnatal days 2-14), which acts against tyrosine kinases, the neonatal stress-induced down-shifted visceral pain threshold was restored and neuronal activation, specifically NGF and neuropeptide production, was attenuated. In conclusion, our data strongly suggest that NGF triggers neuronal plasticity and plays a crucial role in NMS-induced visceral hypersensitivity in which NGF antagonism provides positive inhibition via blocking the tyrosine phosphorylation of TrkA.