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Patients with chronic pain and especially with craniomandibular disorder (CMD) show specific psychopathology in trait anxiety. In a previous longitudinal functional imaging study on CMD we found that the anterior insula was modulated by successful therapy intervention and pain relief. We here intended to investigate possible associations between anterior insula fMRI-activation during occlusal movements and trait anxiety over a splint therapy approach in patients with CMD. Three fMRI-investigations of a craniomandibular occlusion task were performed together with pain score evaluations and scoring of trait anxiety (State -Trait Anxiety Inventory; STAI) before, after two weeks and after three months of a DIR-mandibular splint therapy in a small group (n = 9) of CMD patients. Patients showed increased anxiety levels before therapy assessed with the STAI and the depression and anxiety scale (DASS). Besides of relevant reduction in pain the STAI decreased over time. Reduction in STAI was associated with anterior insular fMRI-activation reduction on both hemispheres. We conclude that the anxiety driven anticipation of pain related to occlusal trigger is processed in the anterior insula and might therefore be a main driver of therapeutic intervention by the splint therapy in CMD.
Learn More >Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.
Learn More >Dorsal root ganglion (DRG) stimulation has been demonstrated to be effective in treating painful diabetic polyneuropathy in a small case series. However, diabetic polyneuropathy only accounts for 41% of all polyneuropathies and the efficacy of DRG on other types of polyneuropathy is unclear. The objective of this study is to evaluate the efficacy of DRG stimulation in treating painful hereditary and idiopathic axonal polyneuropathy.
Learn More >Chronic pain is a debilitating condition of multifactorial origin, often without physical findings to explain the presenting symptoms. Of the possible etiologies of persisting painful symptoms, somatoform disorders and functional somatic syndromes (FSS) are among the most challenging, with a prevalence of 8-20%. Many different somatoform disorders and FSS have overlapping symptoms, with pain being the most prevalent one. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We hypothesized that the concept of MSD will be reflected in a distinct sensory profile of patients compared with healthy controls and possibly provide insight into the type and pathophysiology of the pain commonly experienced by patients.
Learn More >Diffuse noxious inhibitory controls (DNIC) are a mechanism of endogenous descending pain modulation, and are deficient in a large proportion of chronic pain patients. However, the pathways involved remain only partially determined with several cortical and brainstem structures implicated. This study examined the role of the dorsal reticular nucleus (DRt) and infralimbic (ILC) region of the medial prefrontal cortex in DNIC. In vivo electrophysiology was performed to record from dorsal horn lamina V/VI wide dynamic range neurones with left hind paw receptive fields in anaesthetised sham-operated and L5/L6 spinal nerve ligated (SNL) rats. Evoked neuronal responses were quantified in the presence and absence of a conditioning stimulus (left ear clamp). In sham rats, DNIC were reproducibly recruited by a heterotopically applied conditioning stimulus, an effect that was absent in neuropathic rats. Intra-DRt naloxone had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. In addition, intra-DRt naloxone blocked DNIC in sham rats, but had no effect in SNL rats. Intra-ILC lidocaine had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. However, differential effects were observed in relation to the expression of DNIC; intra-ILC lidocaine blocked activation of DNIC in sham rats but restored DNIC in SNL rats. These data suggest that the ILC is not directly involved in mediating DNIC but can modulate its activation, and that DRt involvement in DNIC requires opioidergic signalling.
Learn More >Significant unmet need exists for long-term treatment of moderate-to-severe atopic dermatitis (AD).
Learn More >Background and purpose – Pain catastrophizing contributes to acute and long-term pain after total knee arthroplasty (TKA) but currently there are only limited treatment options. This study investigates the effectiveness of patient education in pain coping among patients with moderate to high pain catastrophizing score before TKA. Secondary outcomes were physical function, quality of life, self-efficacy, and pain catastrophizing.Patients and methods – The study was a parallel-group randomized controlled trial including patients with moderate to high levels of pain catastrophizing. 60 patients were recruited from December 2015 to June 2018. The mean age of the patients was 66 (47-82) years and 40 were women. The patients were randomized to either cognitive-behavioral therapy (CBT) based pain education or usual care. The primary outcome measure was pain under activity measured with the Visual Analog Scale (VAS). All outcomes were measured preoperatively, at 3 months, and at 1 year after surgery.Results – We found no difference in the primary outcome measure, VAS during activity, between the 2 groups but both groups had large reductions over time. The CBT-based pain education group reduced their VAS score by 37 mm (95% CI 27-46) and the control group by 40 mm (CI 31-49). We found no statistically significantly differences between the 2 groups in any of the secondary outcomes.Interpretation – Future research is warranted to identify predictors of persistent pain and interventions for the approximately 20% of patients with persisting pain after a TKA.
Learn More >Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by widespread pain and a variety of non-pain symptoms. Central sensitivity phenomena are found consistently in FMS. Additionally, several researchers proclaimed that a subgroup of FMS patients may present with unrecognized peripheral small fiber neuropathy (SFN). Laser-evoked brain potentials (LEP) are considered as a reliable method for the functional assessment of the thermo-nociceptive system, including the evaluation of SFN.
Learn More >The nitric-oxide donor nitroglycerin (NTG) administration induces a facilitation of nociceptive pathways in episodic migraine. This study aims to test the hypothesis that induced spinal sensitization could be more pronounced in patients affected by high frequency migraine (HF-MIG) respect to low frequency migraine (LF-MIG).We enrolled 28 patients with LF-MIG (1-5 migraine days/month), 19 patients with HF-MIG (6-14 migraine days/month) and 21 healthy controls (HC). Spinal sensitization was evaluated with the neurophysiological recording of the temporal summation threshold (TST) of the nociceptive withdrawal reflex at the lower limb. TST was recorded at baseline and 30, 60 and 120 minutes after NTG administration (0.9 mg sublingual).Spinal sensitization was detected in LF-MIG at 60 (p=0.010) and 120 minutes (p=0.001) and in HF-MIG at 30 (p=0.008), 60 (p=0.001) and 120 minutes (p=0.001) after NTG administration. TST did not change in HC (p=0.899). Moreover, TST reduction was more pronounced in HF-MIG respect to LF-MIG (p=0.002).The percentage of patients who developed a migraine-like headache after NTG was comparable in the two migraine groups (LF-MIG: 53.6%, HF-MIG: 52.6%, p=0.284), while no subjects in HC group developed a delayed-specific headache. Notably, the latency of headache onset was significantly shorter in the HF-MIG group when compared to the LF-MIG group (p=0.015).Our data demonstrate a direct relationship between migraine frequency and both neurophysiological and clinical parameters, to suggest an increasing derangement of the nociceptive system control as the disease progresses, probably as a result of the interaction of genetic and environmental factors.
Learn More >αB-crystallin (CRYAB) is a small heat shock protein that is able to inhibit neuroinflammatory responses under various pathological conditions. Some studies have proven that neuroinflammatory mechanisms play important roles in bone cancer pain (BCP). However, whether CRYAB participates in the maintenance of BCP has not yet been examined.
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