| 1. |
- Kankel, Jennifer, et al.
(författare)
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Differential effects of low dose lidocaine on C-fiber classes in humans
- 2012
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 13:12, s. 1232-1241
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Tidskriftsartikel (refereegranskat)abstract
- The nonselective sodium channel blocker lidocaine is widely used as a local anesthetic but also systemically for treatment of postoperative and neuropathic pain. Voltage-gated sodium channels are crucial for action potential generation and conduction, and their availability controls the amount of activity-dependent conduction velocity slowing. This important axonal property, as assessed by microneurography, is used to differentiate human mechanoinsensitive (silent) nociceptors from the classical polymodal nociceptors. In the current study, microneurography was used to assess axonal properties of the 2 main nociceptor classes in humans, before and after intradermal injection of lidocaine .1% or control saline solution in the receptive field. In mechanosensitive nociceptors, lidocaine reduced baseline conduction velocity and turned activity-dependent slowing into speeding of conduction. In contrast, mechanoinsensitive fibers were not affected in their baseline conduction velocity or their activity-dependent slowing, but probability of conduction block with repetitive stimulation increased. Recovery cycles showed reduced hyperpolarization in all C-fiber classes after lidocaine injections. These results support our hypothesis that sodium channel subtypes are differentially expressed in the 2 nociceptor classes of mechanosensitive C-fibers (CMs) and mechanoinsensitive C-fibers (CMis).Perspective: This study reveals that microneurography can be used to assess pharmacologicaleffects on single C-fibers directly in humans.
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| 2. |
- Kleggetveit, Inge P., et al.
(författare)
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Pathological nociceptors in two patients with erythromelalgia-like symptoms and rare genetic Nav 1.9 variants
- 2016
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear. Methods: C-nociceptors from two patients with late onset of erythromelalgia-like pain, signs of small fiber neuropathy, and rare genetic variants of Nav 1.9 (N1169S, I1293V) were assessed by microneurography. Results: Compared with patients with comparable pain phenotypes (erythromelalgia-like pain without Nav-mutations and painful polyneuropathy), there was a tendency toward more activity-dependent slowing of conduction velocity in mechanoinsensitive C-nociceptors. Hyperexcitability to heating and electrical stimulation were seen in some nociceptors, and other unspecific signs of increased excitability, including spontaneous activity and mechanical sensitization, were also observed. Conclusions: Although the functional roles of these genetic variants are still unknown, the microneurography findings may be compatible with increased C-nociceptor excitability based on increased Nav 1.9 function.
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| 3. |
- Schmidt, Roland, et al.
(författare)
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Double spikes to single electrical stimulation correlates to spontaneous activity of nociceptors in painful neuropathy patients.
- 2012
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 153:2, s. 391-8
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Tidskriftsartikel (refereegranskat)abstract
- Multiple firing of C nociceptors upon a single electrical stimulus has been suggested to be a possible mechanism contributing to neuropathic pain. Because this phenomenon maybe based on a unidirectional conduction block, it might also be related to neuropathic changes without a direct link to pain. We investigated painful neuropathy patients using microneurography and analysed nociceptors for the occurrence of multiple spiking and spontaneous activity. In 11 of 105 nociceptors, double spiking was found, with 1fibre even showing triple spikes on electrical stimulation. The interval between the main action potential and the multiple spikes ranged from 13 to 100ms. There was a significant association between spontaneous activity and multiple spiking in C nociceptors, with spontaneous activity being present in 9 of 11 fibres with multiple spiking, but only in 21 of 94 nociceptors without multiple spiking (P<.005, Fisher exact test). Among the 75 C nociceptors without spontaneous activity, only 2 nociceptors showed multiple spiking. In 8 neuropathy patients without pain, double spiking was found only in 4 of 90 nociceptors. Multiple spiking of nociceptors coincides with spontaneous activity in nociceptors of painful neuropathy patients. We therefore conclude that rather than being a generic sign of neuropathy, multiple spiking is linked to axonal hyperexcitability and spontaneous activity of nociceptors. It is still unclear whether it also is mechanistically related to the clinical pain level.
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| 4. |
- Stjernbrandt, Albin, 1985-
(författare)
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Cold exposure and health : A study on neurological and vascular hand symptoms in northern Sweden
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Living in a cold climate is associated with several adverse health effects. The main purpose of this thesis was to describe cold exposure characteristics in northern Sweden, and investigate the associations between such exposure and the reporting of neurological and vascular hand symptoms. One common cold-related hand symptom is Raynaud’s phenomenon, defined as episodic attacks of acral pallor or cyanosis. There is evidence to suggest that cold exposure can act both as a causal factor and a trigger for such vasospastic symptoms. Other important associated factors include exposure to hand-arm vibration and the presence of rheumatic disease. A somewhat similar clinical entity, cold sensitivity, is defined as a collection of acquired symptoms, resulting in an abnormal aversion to cold, with pain, sensory alterations, stiffness, or color changes, which may occur after a traumatic injury. The condition is hypothesized to mainly originate from nerve injury. The effects of cold exposure on hand function, the occurrence of cold sensitivity in the general population, the link between cold exposure and cold sensitivity, as well as the interface between cold sensitivity and Raynaud’s phenomenon are not fully understood. Therefore, this thesis was also intended to expand the knowledge on Raynaud’s phenomenon and cold sensitivity.Methods: Postal surveys were sent to a sample of men and women between 18 and 70 years of age, living in Norrbotten, Västerbotten, Västernorrland, and Jämtland, drawn from the national Swedish population register. The first survey collected data on 12,627 subjects, and the results were used to describe cold exposure characteristics, and broadly investigate the statistical associations with different neurological and vascular hand symptoms (Paper I). A follow-up survey was sent to a subset of responders, to form nested case–control studies on cold sensitivity (N=1,230; Paper II) and Raynaud’s phenomenon (N=1,400; Paper III). Subjects with cold sensitivity (N=12) from Paper II were subsequently recruited to a laboratory study, to investigate the vascular and neurosensory function of the hands, by means of physical examination, laser speckle contrast analysis before and after cold stress testing, and thermal quantitative sensory testing (Paper IV). Finally, healthy controls (N=1,239) from the case–control studies were used as a reference population for the Cold intolerance symptom severity questionnaire, to establish a cut-off for abnormal cold sensitivity (Paper V).Results: In Paper I, cold exposure was commonly reported, both during work and leisure time. Exposure was most pronounced in alpine regions, generally higher among men than women, and decreased with age. Highly cold-exposed occupational groups were militaries; agricultural, forestry and fishery workers; and crafts and related trades workers (e.g. construction workers). The correlation between occupational and leisure-time cold climate exposure was low. Men reported more occupational exposure to hand-arm vibration than women, but the correlation between occupational cold and vibration exposure was low. A range of neurological and vascular hand symptoms were statistically associated with high cold exposure, such as decreased perception to touch, warmth, and cold, as well as Raynaud’s phenomenon. In Paper II, cold sensitivity was significantly associated with previous frostbite affecting the hands, rheumatic disease, upper extremity nerve injury, migraine, vascular disease, and high body mass index (inversely), in a multiple conditional logistic regression model. In Paper III, Raynaud’s phenomenon was significantly associated with previous frostbite affecting the hands, first degree heredity, and high body mass index (inversely), in a similar model. Previous upper extremity nerve injury was suggested as a separating trait between Raynaud’s phenomenon and cold sensitivity. In Paper IV, laser speckle contrast analysis indicated disturbances in microvascular regulation, while physical examination and thermal quantitative sensory testing mainly yielded normal results. In Paper V, the 95th percentile for the Cold intolerance symptom severity score was 49.5 for men, and 53.0 for women.Conclusions: Cold exposure in the working-age population of northern Sweden varied with age, gender, occupation, and place of residence. Cold exposure was related to the reporting of neurological and vascular hand symptoms in the population as a whole. There was a major overlap between reporting cold sensitivity and Raynaud’s phenomenon, and the conditions shared several associated factors. Previous upper extremity nerve injury was suggested to be a separating trait, supporting the neurosensory pathophysiological hypothesis for cold sensitivity. Cold sensitivity was not effectively assessed by physical examination or thermal quantitative sensory testing. However, laser speckle contrast analysis could prove a useful tool in further studies on cold sensitivity. A Cold intolerance symptom severity score above 50 could be considered to indicate abnormal cold sensitivity, and be used to guide further care.
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