Machine learning suggests sleep as a core factor in chronic pain.

Patients with chronic pain have complex pain profiles and associated problems. Subgroup analysis can help identify key problems. We used a data-based approach to define pain phenotypes and their most relevant associated problems in 320 patients undergoing tertiary pain management.

Voriconazole greatly increases the exposure to oral buprenorphine.

Purpose: Buprenorphine has low oral bioavailability. Regardless of sublingual administration, a notable part of buprenorphine is exposed to extensive first-pass metabolism by the cytochrome P450 (CYP) 3A4. As drug interaction studies with buprenorphine are limited, we wanted to investigate the effect of voriconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics and pharmacodynamics of oral buprenorphine.

Dopaminergic and serotonergic mechanisms in the modulation of pain: In vivo studies in human brain.

Here we review the literature assessing the roles of the brain dopaminergic and serotonergic systems in the modulation of pain as revealed by in vivo human studies using positron emission tomography. In healthy subjects, dopamine D/D receptor availability particularly in the striatum and serotonin 5-HT and 5-HT receptor availabilities in the cortex predict the subject's response to tonic experimental pain. High availability of dopamine D/D or serotonin 5-HT receptors is associated with high pain intensity, whereas high availability of 5-HT receptors associates with low pain intensity.

Acute pain intensity monitoring with the classification of multiple physiological parameters.

Current acute pain intensity assessment tools are mainly based on self-reporting by patients, which is impractical for non-communicative, sedated or critically ill patients. In previous studies, various physiological signals have been observed qualitatively as a potential pain intensity index. On the basis of that, this study aims at developing a continuous pain monitoring method with the classification of multiple physiological parameters.

The association between physicians' attitudes to psychosocial aspects of low back pain and reported clinical behaviour: A complex issue.

Background and aim Physicians' attitudes predict clinical decision making and treatment choices, but the association between attitudes and behaviour is complex. Treatment guidelines for non-specific low back pain (LBP) include recommendations of early assessment of psychosocial risk factors forchronic pain, patient education and reassurance. Implication of these principles is demanding, and many patients are not referred for appropriate treatments due to a lack of systematic screening of psychosocial risk factors for chronic pain.

Psychiatric (axis I) and personality (axis II) disorders in patients with burning mouth syndrome or atypical facial pain.

Background and aims Burning mouth syndrome (BMS) and atypical facial pain (AFP) are often persistent idiopathic pain conditions that mainly affect middle-aged and elderly women. They have both been associated with various psychiatric disorders. This study examined current and lifetime prevalence of psychiatric axis I (symptom-based) and II (personality) disorders in patients with chronic idiopathic orofacial pain, and investigated the temporal relationship of psychiatric disorders and the onset of orofacial pain.

Validation of EQ-5D and 15D in the assessment of health-related quality of life in chronic pain.

Chronic pain has a significant impact on quality of life. Measurement of health-related quality of life (HRQoL) is essential in the assessment of pain management outcomes, but different instruments have produced varying results. We assessed the validity of 2 HRQoL instruments, EuroQol 5 dimensions questionnaire (EQ-5D) and 15-dimensional health-related quality of life measure (15D), in patients with challenging chronic pain.

Rifampicin decreases exposure to sublingual buprenorphine in healthy subjects.

Buprenorphine is mainly metabolized by the cytochrome P450 (CYP) 3A4 enzyme. The aim of this study was to evaluate the role of first-pass metabolism in the interaction of rifampicin and analgesic doses of buprenorphine. A four-session paired cross-over study design was used.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders.

Background: Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS.

[Update on current care guidelines. Pain].

Management of patients suffering from chronic pain is based on long-term therapeutic relationship. The main objectives of the treatment are pain relief, restoration of function and improvement of quality of life. Interventions for treatment and rehabilitation need to be planned in agreement with the patient.

Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy.

Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers.

[Can we prevent pain becoming chronic?].

Central aspects in the prevention of pain from becoming chronic are good management of acute pain, early recognition of risk factors and a multidisciplinary working approach. Postherpetic neuralgia can probably be prevented with a vaccine and medication. In the prevention of prolonged postoperative pains there is some evidence of the effect of local anesthetics and ketamine, but their clinical significance is unclear.

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS.

Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.

Background: Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6.

Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms.

Rifampicin markedly decreases the exposure to oral and intravenous tramadol.

Purpose: Tramadol is mainly metabolized by the cytochrome P450 (CYP) 2D6, CYP2B6 and CYP3A4 enzymes. The aim of this study was to evaluate the effect of enzyme induction with rifampicin on the pharmacokinetics and pharmacodynamics of oral and intravenous tramadol.

Methods: This was a randomized placebo-controlled crossover study design with 12 healthy subjects.

Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction.

Purpose: We assessed possible drug interactions of tramadol given concomitantly with the potent CYP2B6 inhibitor ticlopidine, alone or together with the potent CYP3A4 and P-glycoprotein inhibitor itraconazole.

Methods: In a randomized, placebo-controlled cross-over study, 12 healthy subjects ingested 50 mg of tramadol after 4 days of pretreatment with either placebo, ticlopidine (250 mg twice daily) or ticlopidine plus itraconazole (200 mg once daily). Plasma and urine concentrations of tramadol and its active metabolite O-desmethyltramadol (M1) were monitored over 48 h and 24 h, respectively.

Rifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine.

Low-dose ketamine is currently used in several acute and chronic pain conditions as an analgesic. Ketamine undergoes extensive metabolism and is thus susceptible to drug-drug interactions. We examined the effect rifampicin, a well-known inducer of many cytochrome P450 (CYP) enzymes and transporters, on the pharmacokinetics of intravenous and oral S-ketamine in healthy volunteers.

Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects.

Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects.

S-ketamine concentrations are greatly increased by grapefruit juice.

Purpose: We examined the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral S-ketamine.

Methods: A randomized crossover open-label study design with two phases at an interval of 4 weeks was conducted in 12 healthy volunteers. Grapefruit juice or water was ingested 200 ml t.

St John's wort greatly decreases the plasma concentrations of oral S-ketamine.

Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days.