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1.  Cerebral Activation during Von Frey Filament Stimulation in Subjects with Endothelin-1-Induced Mechanical Hyperalgesia: A Functional MRI Study 
BioMed Research International  2013;2013:610727.
Endothelin-1 (ET-1) is an endogenously expressed potent peptide vasoconstrictor. There is growing evidence that ET-1 plays a role in the pain signaling system and triggers overt nociception in humans. The underlying neuronal pathways are still a matter of great debate. In the present study, we applied an intradermal ET-1 sensitization model to induce mechanical hyperalgesia in healthy subjects. Functional magnetic resonance imaging (fMRI) was used to tease out the cortical regions associated with the processing of ET-1-induced punctate hyperalgesia, as compared to a nonnoxious mechanical stimulation of the contralateral arm. Von Frey hair testing revealed the presence of increased responsiveness to punctate stimulation in all subjects. Activational patterns between nonpainful control stimulation and hyperalgesic stimulation were compared. Two major observations were made: (1) all cortical areas that showed activation during the control stimulation were also present during hyperalgesic stimulation, but in addition, some areas showed bilateral activation only during hyperalgesic stimulation, and (2) some brain areas showed significantly higher signal changes during hyperalgesic stimulation. Our findings suggest that injection of ET-1 leads to a state of punctate hyperalgesia, which in turn causes the activation of multiple brain regions. This indicates that ET-1 activates an extended neuronal pathway.
PMCID: PMC3789290  PMID: 24151613
2.  Outcome predictors for treatment success with 5% lidocaine medicated plaster in low back pain with neuropathic components and neuropathic pain after surgical and nonsurgical trauma 
Journal of Pain Research  2011;4:25-38.
Five percent lidocaine medicated plaster has been proven efficacious for the symptomatic relief of neuropathic pain in diverse pain conditions which might be attributed to a common localized symptomatology in these indications, possibly with common predictors of treatment success. To discuss potential symptoms and other factors predicting response to treatment with lidocaine plaster for the indications of low back pain with neuropathic components and neuropathic pain after surgical and nonsurgical trauma, 44 pain specialists from 17 countries attended a two-day conference meeting in December 2009. Discussions were based on the retrospective analysis of case reports (sent in by participants in the four weeks prior to the meeting) and the practical experience of the participants. The results indicate some predictors for success with 5% lidocaine medicated plaster for the two indications. Localized pain, hyperalgesia and/or allodynia, and other positive sensory symptoms, such as dysesthesia, were considered positive predictors, whereas widespread pain and negative sensory symptoms were regarded as negative predictors. Paresthesia, diagnosis, and site of pain were considered to be of no predictive value. Common symptomatology with other neurologic pathologies suggests that treatment of localized neuropathic pain symptoms with the plaster can be considered across different neuropathic pain indications.
PMCID: PMC3048580  PMID: 21386952
lidocaine plaster; low back pain; surgical and nonsurgical trauma pain; neuropathic pain; case report
3.  Lidocaine 5% patch for localized neuropathic pain: progress for the patient, a new approach for the physician 
Neuropathic pain (NeP) syndromes remain a difficult-to-treat medical entity. Despite a growing number of pharmacological and invasive analgesic therapies the results remain less than optimal because of insufficient analgesic efficacy and/or occurrence of pronounced side effects. Current guidelines propose the use of multimodal and balanced pharmacological therapies, focused on the underlying pathophysiological mechanisms (mechanistic approach). Lidocaine 5% patches are a new treatment option currently licensed for the treatment of postherpetic neuralgia. However, these patches can also be used for the treatment of different types of superficial NeP syndromes, such as diabetic polyneuropathy. Their therapeutic success, however, largely depends on the correct identification of appropriate patients and pain syndromes. This manuscript outlines the correct identification of patients and proper use of these patches in order to ensure as much as possible the therapeutic efficacy of this new treatment option.
PMCID: PMC3262358  PMID: 22291487
neuropathic pain; lidocaine; patch
4.  Transdermal buprenorphine – a critical appraisal of its role in pain management 
Journal of pain research  2009;2:117-134.
This paper reviews the current clinical data for the role of transdermal buprenorphine (BUP TDS) in the treatment of diverse acute and chronic pain syndromes. Literature searches were carried out using PubMed (1988 to June 2009). The published findings seem to support hypotheses regarding the rather unique analgesic mechanisms of buprenorphine as compared with pure μ-opioids like morphine and fentanyl. However, the exact mechanism of this analgesic efficacy still remains largely unknown despite recent advances in preclinical pharmacological studies. Such assessments have demonstrated the sustained antihyperalgesic effect of buprenorphine in diverse animal pain models. These findings are supported in a growing number of clinical studies of oral, intrathecal, intravenous, and Bup TDS. This review paper focuses almost entirely on the clinical experience concerning the transdermal administration of buprenorphine, although preclinical aspects are also addressed in order to provide a complete picture of the unique pharmacological properties of this analgesic drug. Mounting evidence indicates the appropriateness of Bup TDS in the treatment of diverse acute and chronic pain syndromes which have been less or not responsive to other opioids. Additionally, BUP TDS seems to hold great promise for other difficult-to-treat (pain) conditions, such as patients in the intensive care setting. However, its use is somewhat tempered by the occurrence of local skin reactions which have been shown to be often therapy resistant. Further studies are certainly warranted to identify even more precisely the clinical syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine to other opioids in head-to-head trials of acute and chronic pain conditions.
PMCID: PMC3004620  PMID: 21197300
buprenorphine; transdermal; opioids; pain
5.  Altered sensitivity to mechanical stimulation during prolonged subcutaneous administration of endothelin-1 in rats 
Journal of pain research  2009;2:67-73.
Cancer pain is often difficult to treat. Growing evidence indicates that chemical mediators secreted by the tumor itself play an important role in the development of cancer pain. One such mediator, endothelin-1 (ET-1) is secreted by different tumor types. Studies have indicated that ET-1 induces spontaneous and evoked nociception in rodents and in humans. The focus of all these studies has always been on a single administration of ET-1. Such an acute exposure to ET-1 however bears little resemblance to the clinical condition in which cancer patients are exposed continuously for many months to increased levels of ET-1. To improve the knowledge of the pathological role of ET-1 in cancer, we developed an animal model of prolonged exposure to ET-1. Rats were exposed to subcutaneous administration of ET-1 for seven consecutive days, with a total amount of 67.4 nmol. On days +2, +3, +5, +7, and +10 sensitivity to von Frey hairs and to pin-prick stimulation were evaluated. Prolonged administration of ET-1 induced signs of mechanical allodynia on several time points. Although the administered doses were very small, prolonged administration of ET-1 seems to lead to a state of mechanical allodynia.
PMCID: PMC3004627  PMID: 21197295
endothelin-1; rat; chronic administration; von Frey hair; pin-prick; mechanical allodynia
6.  The diagnosis and management of neuropathic pain in daily practice in Belgium: an observational study 
BMC Public Health  2007;7:170.
This open, multicentre, observational survey investigated how physicians diagnose neuropathic pain (NeP) by applying the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, and how neuropathic pain conditions are managed in daily practice in Belgium.
Physicians were asked to complete the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale for diagnosing NeP, and to fill out a questionnaire regarding the management of NeP, together with a questionnaire evaluating the impact of pain on sleep and daily life. Data on 2,480 pain patients were obtained. A LANSS score ≥ 12 (meaning NeP is most probably present) was reported for 1,163 patients. Pathologies typically associated with NeP scored above 12 on the LANSS scale, contrary to pathologies generally considered as being of non-neuropathic origin.
Over 90% of the patients with a LANSS score ≥ 12 reported that the pain impaired sleep. A high impact on social, family and professional life was also recorded. Additional examinations were performed in 89% of these patients. Most patients were taking multiple drugs, mainly paracetamol and non-steroidal anti-inflammatory drugs, indicating that physicians generally tend to follow treatment guidelines of chronic nociceptive pain, rather than the specific ones for NeP. Specific neuropathic guidelines rather recommend the use of anti-epileptic drugs, tricyclic antidepressants or weak opioids as first-line treatment.
In our survey, application of the LANSS scale lead to pronounced treatment simplification with fewer drug combinations. Awareness about NeP as well as its specific treatment recommendations should be raised among healthcare providers. We concluded that the LANSS screening scale is an interesting tool to assist physicians in detecting NeP patients in routine clinical care.
PMCID: PMC1947963  PMID: 17650299

Results 1-6 (6)