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Side effects are frequent in pharmacological pain management, potentially preceding analgesia and limiting drug tolerability. Discussing side effects is part of informed consent, yet can favor nocebo effects. This study aimed to test whether a positive suggestion regarding side effects, which could act as reminders of the medication having been absorbed, might favor analgesia in a clinical interaction model. Sixty-six healthy males participated in a study "to validate pupillometry as an objective measure of analgesia". Participants were unknowingly randomized double-blind to positive vs control information about side effects embedded in a video regarding the study drugs. Sequences of moderately painful heat stimuli applied before and after treatment with diclofenac and atropine served to evaluate analgesia. Atropine was deceptively presented as a co-analgesic, but used to induce side effects. Adverse events (AE) were collected with the General Assessment of Side Effects (GASE) questionnaire prior to the second induced pain sequence. Debriefing fully informed participants regarding the purpose of the study and showed them the two videos.The combination of medication led to significant analgesia, without a between-group difference. Positive information about side effects increased the attribution of AE to the treatment compared to the control information. The total GASE score was correlated with analgesia, i.e., the more AEs reported, the stronger the analgesia. Interestingly, there was a significant between-groups difference on this correlation: the GASE score and analgesia correlated only in the positive information group. This provides evidence for a selective link between AEs and pain relief in the group who received the suggestion that AEs could be taken as a sign "that help was on the way". During debriefing, 65% of participants said they would prefer to receive the positive message in a clinical context. Although the present results cannot be translated immediately to clinical pain conditions, they do indicate the importance of testing this type of modulation in a clinical context.
Learn More >Cranial allodynia associated with spontaneous migraine is reported as either responsive to triptan treatment or to be predictive of lack of triptan efficacy. These conflicting results suggest that a single mechanism mediating the underlying neurophysiology of migraine symptoms is unlikely. The lack of a translational approach to study cranial allodynia reported in migraine patients is a limitation in dissecting potential mechanisms. Our objective was to study triptan-responsive cranial allodynia in migraine patients, and to develop an approach to studying its neural basis in the laboratory. Using nitroglycerine to trigger migraine attacks, we investigated whether cranial allodynia could be triggered experimentally, observing its response to treatment. Preclinically, we examined the cephalic response properties of central trigeminocervical neurons using extracellular recording techniques, determining changes to ongoing firing and somatosensory cranial-evoked sensitivity, in response to nitroglycerine followed by triptan treatment. Cranial allodynia was triggered alongside migraine-like headache in nearly half of subjects. Those who reported cranial allodynia accompanying their spontaneous migraine attacks were significantly more likely to have symptoms triggered than those that did not. Patients responded to treatment with aspirin or sumatriptan. Preclinically, nitroglycerine caused an increase in ongoing firing and hypersensitivity to intracranial-dural and extracranial-cutaneous (noxious and innocuous) somatosensory stimulation, reflecting signatures of central sensitization potentially mediating throbbing headache and cranial allodynia. These responses were aborted by a triptan. These data suggest that nitroglycerine can be used as an effective and reliable method to trigger cranial allodynia in subjects during evoked migraine, and the symptom is responsive to abortive triptan treatments. Preclinically, nitroglycerine activates the underlying neural mechanism of cephalic migraine symptoms, central sensitization, also predicting the clinical outcome to triptans. This supports a biological rationale that several mechanisms can mediate the underlying neurophysiology of migraine symptoms, with nitrergic-induced changes reflecting one that is relevant to spontaneous migraine in many migraineurs, whose symptoms of cranial allodynia are responsive to triptan treatment. This approach translates directly to responses in animals and is therefore a relevant platform to study migraine pathophysiology, and for use in migraine drug discovery.
Learn More >Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear.
Learn More >Chronic pain, such as low-back pain, can be a highly disabling condition degrading people's quality of life (QoL). Not every patient responds to pharmacological therapies, thus alternative treatments have to be developed. The chronicity of pain can lead to a somatic dysperception, meaning a mismatch between patients' own body perception and its actual physical state. Since clinical evaluation of pain relies on patients' subjective reports, a body image disruption can be associated with an incorrect pain rating inducing incorrect treatment and a possible risk of drug abuse. Our aim was to reduce chronic low-back pain through a multimodal neurorehabilitative strategy using innovative technologies to help patients regain a correct body image.
Learn More >High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identification of treatment predictors. Additionally, the study identified baseline-characteristics in chronic low back pain patients prior to tapentadol PR treatment, as well as scrutinized those patients, either benefitting from a medium/high dose tapentadol PR monotherapy or a combination therapy (medium dose tapentadol PR + pregabalin). The statistical approach included data of a previously published randomized, double blind, phase 3b study which compared the effectiveness and safety of tapentadol PR vs. a combination of tapentadol PR and pregabalin. In total, 46 clinical parameters were included in the statistical prediction models which were applied separately either to 50 patients who already responded well during the titration period (i.e., medium dose tapentadol PR) or to 261 patients with in the comparative treatment period [i.e., monotherapy (high dose tapentadol PR) or combination therapy (medium dose tapentadol PR/pregabalin)]. The first statistical model identified three co-variables (NRS-3, PDQ, SQ) with predictive effects on patients responding well ("optimal responders") to a medium dose tapentadol PR titration. Those patients presented low baseline pain intensity scores, good sleep quality and high painDETECT scores. The second statistical model identified eight co-variables (PDQ, numbness, SF-12 MCS, SF-12 PCS, VAS, HADS-A, HADS-D, SQ) with predictive effects on patients responding to high dose tapentadol PR monotherapy vs. a combination therapy (tapentadol PR + pregabalin). The high dose tapentadol PR responders indicated high painDETECT scores, little numbness and a good mental health status. Whereas, the combination therapy (tapentadol PR + pregabalin) responders were characterized by severe sleep disturbances and little anxiety. The statistical analysis characterized chronic low back pain patients and identified factors contributing to a treatment response. Thus, this retrospective statistical algorithm represents an elegant method, which may contribute to future strategies toward a more individualized and improved mechanism based pain therapy.
Learn More >Trigeminal Neuralgia (TN) is a chronic neuropathic pain syndrome characterized by paroxysmal unilateral shock-like pains in the trigeminal territory most frequently attributed to neurovascular compression of the trigeminal nerve at its root entry zone. Recent advances in the study of TN suggest a possible central nervous system (CNS) role in modulation and maintenance of pain. TN and other chronic pain patients commonly experience alterations in cognition and affect, as well as abnormalities in CNS volume and microstructure in regions associated with pain perception, emotional modulation, and memory consolidation. However, the microstructural changes in the hippocampus, an important structure within the limbic system, have not been previously studied in TN patients. Here, we use grey matter analysis to assess whether TN pain is associated with altered hippocampal subfield volume in patients with classic TN. Anatomical magnetic resonance (MR) images of twenty-two right-sided TN patients and matched healthy controls underwent automated segmentation of hippocampal subfields using FreeSurfer v6.0. Right-sided TN patients had significant volumetric reductions in ipsilateral cornu ammois 1 (CA1), CA4, dentate gyrus, molecular layer, and hippocampus-amygdala transition area – resulting in decreased whole ipsilateral hippocampal volume, compared to healthy controls. Overall, we demonstrate selective hippocampal subfield volume reduction in patients with classic TN. These changes occur in subfields implicated as neural circuits for chronic pain processing. Selective subfield volume reduction suggests aberrant processes and circuitry reorganization, which may contribute to development and/or maintenance of TN symptoms.
Learn More >Chronic neuropathic pain (NP) is a complex disease that results from damage or presumed damage to the somatosensory nervous system. Current treatment regimens are often ineffective. The major impediment in developing effective treatments is our limited understanding of the underlying mechanisms. Preclinical evidence suggests that glial changes are crucial for the development of NP and a recent study reported oscillatory activity differences within the ascending pain pathway at frequencies similar to that of cyclic gliotransmission in NP. Furthermore, there is evidence that glial modifying medications may be effective in treating NP. The aim of this Phase I open-label clinical trial is to determine whether glial modifying medication palmitoylethanolamide (PEA) will reduce NP and whether this is associated with reductions in oscillatory activity within the pain pathway. We investigated whether 6 weeks of PEA treatment would reduce pain and infra-slow oscillatory activity within the ascending trigeminal pathway in 22 individuals (17 females) with chronic orofacial NP. PEA reduced pain in 16 (73%) of the 22 subjects, 11 subjects showed pain reduction of over 20%. Whilst both the responders and non-responders showed reductions in infra-slow oscillatory activity where orofacial nociceptor afferents terminate in the brainstem, only responders displayed reductions in the thalamus. Furthermore, functional connections between the brainstem and thalamus were altered only in responders. PEA is effective at relieving NP. This reduction is coupled to a reduction in resting oscillations along the ascending pain pathway that are likely driven by rhythmic astrocytic gliotransmission.
Learn More >The newly developed calcitonin gene-related peptide (CGRP) antagonists were recently launched on the US and European market, with Switzerland as the second country worldwide. To enable forthcoming comparisons with established migraine therapy, the aim of this study was to provide a comprehensive picture of migraine (prophylactic) treatment patterns. Recent data in daily clinical practice are lacking.
Learn More >RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities.
Learn More >Persistent idiopathic facial pain (PIFP) is a subtype of painful cranial neuropathies and other facial pains. The involvement of neuropathic mechanisms in PIFP, however, remains controversial. Using the Douleur Neuropathique 4 (DN4) questionnaire, the present study examined neuropathic characteristics in patients with PIFP.
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