Comparing sensibility for touch, cold, and warmth in different skin areas.

The primary objective of this pilot study was to assess if the magnitude estimation of suprathreshold brushing, warmth (40 °C), and cold (25 °C) stimuli of the skin over the dorsum of the hand and the dorsum of the foot are comparable to the perceived intensity for the same stimuli applied to the skin over any of the following areas: forehead, m. trapezius, m. deltoideus, thoracic back, and lumbar back, respectively. Thirty-two subjects aged 18-64 years were included. Participants were examined by two physicians on two different occasions, 1-58 days apart. Participants rated the magnitude of the perceived sensation of each stimulus on an 11-point numerical rating scale (NRS) 0-10, where 0 was anchored to "no sensation at all for touch/cold/warmth" and 10 anchored to "the most intense imaginable non-painful sensation of touch/cold/warmth". The criterion for sensory equivalence for one modality was arbitrarily considered satisfactory if two regions had the same numerical rating ±1 point in at least 85% of the individuals. Based on the pre-study criteria for sensory equivalence applied in this study only one area was found to be equivalent to the foot skin for the percept of brushing, that is, the skin over the deltoid muscle and one area for the hand, that is, the skin over the forehead. We failed to find any area with equivalent sensitivity to the hand or the foot for the cold or warm stimuli.

The perception threshold counterpart to dynamic and static mechanical allodynia assessed using von Frey filaments in peripheral neuropathic pain patients.

Background and aim Pain due to a usually non-painful mechanical stimulus, mechanical allodynia, is an oppressive symptom in subgroups of patients with neuropathic pain. Dynamic mechanical allodynia (DMA) is evoked by a normally innocuous light moving mechanical stimulus on the skin and static mechanical allodynia (SMA) by a sustained, normally innocuous pressure against the skin. DMA is claimed to be mediated by myelinated fibres and SMA by C-fibres. Also A-delta fibres have been implicated in the static subtype. A low intensity vertically applied stimulus of 1 second (s) is expected to activate predominantly rapidly adapting A-beta mechanoreceptors thus recruiting the same peripheral substrate as a horizontally moving brush on top of the skin. In patients with SMA we assumed an activation of Cbut also A-delta fibres from a static 10 s von Frey filament stimulus. The aim was to investigate if DMA and SMA could be assessed at perception threshold level using short or longer lasting usually non-painful von Frey filament prodding of the neuropathic skin. Patients and methods Eighteen patients with painful unilateral partial peripheral traumatic nerve injury suffering from SMA (n = 9) and/or DMA (n = 18) in a limb were studied. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to pain at perception threshold level using 1 s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin. Results The main outcome was the finding that elevation of vF1 and vF10 occurred simultaneously and significantly prior to an increase in the perception level to cold or warmth during the continuous nerve block. Single patients demonstrated a slight decrease in cold perception levels at the time of elevation of vF1 or vF10 and a possible contribution to mechanical allodynia from A-delta-fibres can therefore not completely be ruled out although the recorded alterations were minor. None of the patients reported an elevation of the perception level to warmth at the time of elevation of vF1 or vF10 excluding contribution from C-fibres. Further, only patients with clinically established SMA (n = 9) reported continuous pain to a sustained 10 s von Frey filament stimulation (vF10). Patients with only DMA (n = 9) reported pain merely for the initial 1-3 s of the total stimulus duration of 10 s and for a few seconds after the filament was lifted from the skin. Conclusions These findings support the role of A-beta fibres as peripheral mediators of both vF1 and vF10 although different receptor organs may be involved, i.e., rapidly (RA) and slowly (SA-I) adapting mechanoreceptors. Implications Techniques to quantify the different allodynias at perception threshold level deserve further attention as possible adjuncts to suprathreshold stimuli in intervention studies aimed at modifying these stimulus-evoked phenomena.

Mechanisms of dynamic mechanical allodynia and dysesthesia in patients with peripheral and central neuropathic pain.

Eighteen patients with peripheral neuropathic pain (PNeP) and seven patients with central post-stroke pain (CPSP) all suffering from dynamic mechanical allodynia (DMA) in a limb were studied. From recent research it is reasonable to suggest that A-beta fibres constitute the peripheral substrate for DMA in patients with PNeP. The pathophysiological basis for DMA in patients with CPSP is unknown. It is clinically observed that some patients with neuropathic pain report variable intensity of DMA and volunteer that the phenomenon at times is only an unpleasant, i.e., dysesthetic sensation. The pathophysiological basis for dynamic mechanical dysesthesia (DMD) has never been addressed. Based on the aforementioned clinical observations we aimed at investigating if DMA is the hyperbole of DMD both mediated by A-beta fibres in the periphery. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to DMA and DMD, respectively. During the nerve block there was a transition of DMA to DMD in all patients with PNeP and in 3/7 patients with CPSP. The rest of the patients lost DMA without transition to DMD. The transition or loss of DMA without transition occurred early and concurrently in time during the block and was paralleled by a continuous impairment of mainly A-beta fibre function. We therefore suggest DMA to be the hyperbole of DMD, the difference being the number of mechanoreceptive fibres having access to the nociceptive system.

Somatosensory function in patients with and without pain after traumatic peripheral nerve injury.

Why traumatic injuries to the peripheral nervous system infrequently result in neuropathic pain is still unknown. The aim of this study was to examine the somatosensory system in patients with traumatic peripheral nerve injury with and without pain to try to unravel possible links to mechanisms underlying development and maintenance of pain. Eighteen patients with spontaneous ongoing pain and 16 patients without pain after unilateral partial peripheral traumatic nerve injury were studied. In the area of partial denervation and in the corresponding contralateral area perception thresholds to warmth, cold, light touch, pressure pain, cold- and heat pain were assessed as were pain intensities at suprathreshold heat pain stimulation. Comparing sides patients with pain reported allodynia to cold (p=0.03) and pressure (p=0.016) in conjunction with an increase in the perception threshold to non-painful warmth (p=0.024) on the injured side. Pain-free patients reported hypoesthesia to light touch (p=0.002), cold (p=0.039) and warmth (p=0.001) on the injured side. There were no side differences in stimulus-response functions using painful heat stimuli in any of the groups. In addition, no significant difference could be demonstrated in any sensory modality comparing side-to-side differences between the two groups. In conclusion, increased pain sensitivity to cold and pressure was found on the injured side in pain patients, pointing to hyperexcitability in the pain system, a finding not verified by a more challenging analysis of side-to-side differences between patients with and without pain.

The burden of neuropathic pain: a systematic review and meta-analysis of health utilities.

Patients with neuropathic pain (NeuP) experience substantially lower health-related quality of life (HRQoL) than the general population. The aim of this systematic review and meta-analysis is to test the hypothesis that NeuP is associated with low levels of health utility. A structured search of electronic databases (MEDLINE, EMBASE, Cochrane Library and CINAHL) was undertaken. Reference lists of retrieved reports were also reviewed. Studies reporting utility single-index measures (preference based) in NeuP were included. Random effects meta-analysis was used to pool EQ-5D index utility estimates across NeuP conditions. The association of utilities and pre-defined factors (NeuP condition, patient age, sex, duration and severity of pain and method of utility scoring) was examined using meta-regression. Twenty-four studies reporting health utility values in patients with NeuP were included in the review. Weighted pooled utility score across the studies varied from a mean of 0.15 for failed back surgery syndrome to 0.61 for post-herpetic neuralgia and diabetic neuropathy. Although there was substantial heterogeneity (P<0.0001) across studies, we found little variation in utility as a function of patient and study characteristics. The single exception was a significant relationship (P<0.0001) between increasing neuropathic pain severity and a reduction in utility. This study confirms the hypothesis that patients with NeuP experience low utilities and therefore low HRQoL. However, the contribution of non-NeuP co-morbidity remains unclear. Neuropathic pain severity emerged as a primary predictor of the negative health impact of NeuP.

Assessment of neuropathic pain in primary care.

Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment. In clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care; assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and establishing a rational treatment plan.