Role of burn severity and posttraumatic stress symptoms in the co-occurrence of itch and neuropathic pain after burns: A longitudinal study.

Itch and pain are common after burns. Neuropathic mechanisms may underlie both modalities but remain not well-understood. This study aims to prospectively document neuropathic pain symptoms and to identify potential itch symptom profiles that differ regarding duration and co-occurrence with neuropathic pain which may inform underlying pathophysiological mechanisms and respond to different treatments. Adult burn survivors (n = 192) self-reported itch and neuropathic pain at 2 weeks post-discharge, 3, 6, 12, and 18 months post-burn. Based on the presence of itch and pain symptoms over time, participants were allocated to one itch profile: transient itch/pain, chronic itch, or chronic itch & pain. Profiles were compared on itch intensity over time using General Linear Modeling. Age, gender, burn severity, posttraumatic stress (PTS) symptoms and baseline itch intensity were examined as potential predictors of the profiles in a Multi-nominal regression analysis. Neuropathic pain occurred in 54% after discharge which decreased to 24% 18 months later. Itch intensity was highest in the chronic itch & pain profile. Compared to the transient itch profile, the chronic itch & pain profile was associated with higher burn severity and more PTS symptoms. Compared to the chronic itch profile, the chronic itch & pain profile was associated with more PTS symptoms. Findings suggest that biological and psycho-dermatological processes underlie both chronic neuropathic pain and itch processes in burn scars. Further research should elucidate the mechanisms underlying the different itch profiles, with specific focus on skin innervation and psychological factors.

[Placebo and nocebo effects on itch : Methodological and clinical implications]. / Placebo- und Noceboeffekte bei Pruritus : Methodologische und klinische Implikationen.

Patients often experience positive (placebo) or negative (nocebo) treatment effects due to the positive or negative expectations they have about the treatment. Placebo and nocebo effects have only relatively recently received attention for itch. Experimental studies indicate that, in line with research in other areas, such as pain, learning via verbal suggestion and conditioning plays a key role in placebo and nocebo effects on itch. Results on contagious itch emphasize the role of observational learning and suggest that itch sensations might be particularly susceptible to suggestion and therefore placebo and nocebo effects. Substantial itch reductions in the placebo arms of clinical trials suggest that placebo effects are also important for clinical practice. In this article, an overview is given of how placebo and nocebo effects on itch can optimally be used in research and for the treatment of itch.

Expectations about the effectiveness of pain- and itch-relieving medication administered via different routes.

BACKGROUND: Placebo effects on pain have been found to vary in size for different routes of medication administration (e.g. oral vs. injection). This has important implications for both clinical research and practice. To enhance our understanding of these differential placebo effects, research on the underlying expectations about multiple routes and symptoms other than pain is vital. METHODS: A cross-sectional, Internet-based survey was conducted in a representative sample of the Dutch population (n = 508). Respondents rated the expected effectiveness of pain- and itch-relieving medication in six forms, representing oral, injection and topical routes of administration. RESULTS: Injected medication was expected to be most effective for relieving pain, and topical medication for relieving itch. Furthermore, exploratory analyses showed that injections were expected to have the most rapid onset and long-lasting effects, and to be most frightening and expensive, while topical medication was expected to be the safest and the easiest to use, and oral medication was expected to have the most side effects. Higher expected effectiveness was moderately associated with expectations of more rapid onset and long-lasting effects, and better safety and ease of use. Associations of expected effectiveness with respondent characteristics (e.g. medication use and personality characteristics) were statistically small or nonsignificant. CONCLUSIONS: Expected effectiveness of medication differed depending on route of administration and targeted symptom. These findings have important implications for the design and interpretation of clinical trials and suggest that medication effects might be enhanced by prescribing medicine via the route that patients expect to be most effective for their complaint. SIGNIFICANCE: Differences in the expected effectiveness of medication depend on the route of administration (oral, injection, topical) and targeted symptom (pain, itch). These findings have important implications for clinical practice and the design and interpretation of clinical trials.

Attentional processing of itch.

Itch is a prevalent somatosensory symptom that can be highly disabling, because it is likely to draw attention and, as a result, may interfere with the performance of daily activities. Yet, research experimentally investigating attention to itch is lacking. In this study we aimed to investigate attentional processing of itch using multiple behavioral attention tasks. Forty-one healthy participants performed (1) a modified Stroop task with itch-related words, (2) a dot-probe task with itch-related pictures, and (3) a recently developed somatosensory attention task in which the effect of experimentally induced itch on the localization of visual targets was examined. Additionally, a number of self-report questionnaires related to somatosensory attentional processing were administered. Results indicated that participants' attention was biased toward itch-related words and pictures assessed by means of the dot-probe and modified Stroop task, respectively. For the somatosensory attention task, results showed that itch did not significantly influence the allocation of attention. However, when taking into account the time course of attention during the itch stimulus, data suggested that participants tended to disengage attention away during the itch stimulus. This is the first study that indicates an attentional bias for itch, using methods that have previously been validated for other sensations such as pain. In addition, the newly developed somatosensory attention task may reflect the time course of attention toward a tonic itch stimulus.

Placebo-like analgesia via response imagery.

BACKGROUND: Placebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by instructions, prior experiences and observation of others. Whether mental imagery of a response can also induce placebo-like expectancy effects on pain has not yet been studied systematically. METHODS: In Study 1, 80 healthy participants were randomly allocated to (i) response imagery or (ii) control imagery. In Study 2, 135 healthy participants were randomly allocated to (i) response imagery with a verbal suggestion regarding its effectiveness, (ii) response imagery only, or (iii) no intervention. In both studies, expected and experienced pain during cold pressor tests were measured pre- and post-intervention, along with psychological and physiological measures. RESULTS: Participants rated pain as less intense after response imagery than after control imagery in Study 1 (p = 0.044, ηp2 = 0.054) and as less intense after response imagery (with or without verbal suggestion) than after no imagery in Study 2 (p < 0.001, ηp2 = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068, ηp2 = 0.038). The effects of response imagery on experienced pain were mediated by expected pain. CONCLUSIONS: Thus, in line with research on placebo effects, the current findings indicate that response imagery can induce analgesia, via its effects on response expectancies. SIGNIFICANCE: The reported studies extend research on placebo effects by demonstrating that mental imagery of reduced pain can induce placebo-like expectancy effects on pain.

Role of induced negative and positive emotions in sensitivity to itch and pain in women.

BACKGROUND: Itch and pain are common symptoms in skin disease. It has been suggested that negative emotions may play a role in itch and pain. To date, however, the role of emotions has only been studied for pain in experimental studies, not yet for itch. OBJECTIVES: To investigate the effects of negative and positive emotions on the sensitivity to itch and pain. METHODS: Film fragments were used to induce a negative or positive emotional state in healthy women. Itch and pain were induced using the following somatosensory stimuli: electrical stimulation, histamine iontophoresis and the cold pressor test. RESULTS: Results showed that the scores for itch and pain evoked by histamine and the cold pressor test, respectively, were significantly higher in the negative than in the positive emotion condition, whereas tolerance thresholds to electrical stimulation and the cold pressor test, and stimulus unpleasantness scores did not differ between the two conditions. CONCLUSIONS: These findings for the first time indicate in an experimental design that emotions play a role in sensitivity to somatosensory sensations of both itch and pain.

Induction of protoporphyrin IX by aminolaevulinic acid in actinic keratosis, psoriasis and normal skin: preferential porphyrin enrichment in differentiated cells.

BACKGROUND: In photodynamic therapy the endogenous photosensitizer protoporphyrin IX (PpIX) is synthesized following topical application of aminolaevulinic acid (ALA). However, different tissues have distinct PpIX-accumulating properties, due to differences in penetration of ALA through the stratum corneum and/or alterations in the haem cycle. Preferential PpIX accumulation has been reported in terminally differentiated cell cultures but ex vivo data are lacking. OBJECTIVES: To study the intrinsic PpIX-accumulating capabilities of skin explants from lesional and nonlesional skin in psoriasis and actinic keratosis, with normal skin serving as a control, and to study PpIX accumulation in relation to differentiation status in normal skin. METHODS: Skin explants from patients with psoriasis, actinic keratosis and normal skin were incubated with ALA and PpIX was measured spectrofluorometrically. PpIX was measured in basal (beta1-integrin-positive) and suprabasal (beta1-integrin-negative) keratinocytes in normal skin. In addition, PpIX accumulation was studied in cell cultures at different levels of confluence and after induction of terminal differentiation. RESULTS: No significant differences in PpIX content were found between the different tissues. However, increased PpIX was found in beta1-integrin-negative compared with beta1-integrin-positive cells. In addition, in subconfluent cell cultures less PpIX was found compared with confluent cell cultures. Induction of terminal differentiation in vitro, however, resulted in less PpIX, which was likely to be related to cell volume. CONCLUSIONS: As no significant differences in PpIX synthesis could be found between the different tissue types, these data emphasize the importance of the penetration route of ALA through the stratum corneum. Preferential PpIX accumulation observed in suprabasal epidermal keratinocytes and confluent cell cultures points towards a terminal differentiation-specific effect.

Generalized and symptom-specific sensitization of chronic itch and pain.

BACKGROUND: Physicians are frequently confronted with patients reporting severe itch and pain. Particularly in patients suffering from persistent itch and pain, central and peripheral sensitization processes are assumed to be involved in the long-term maintenance and aggravation of the symptoms. The present study explores generalized and symptom-specific sensitization processes in patients suffering from persistent itch and pain. Specifically, it examines whether patients with chronic itch and pain are more sensitive to somatosensory stimuli (generalized sensitization) and simultaneously perceive somatosensory stimuli as a symptom of their main physical complaint, e.g. pain in chronic pain patients (symptom-specific sensitization). METHODS: Thresholds for different mechanical and electrical sensory stimuli of Quantitative Sensory Testing were determined in 15 female patients suffering from chronic itch associated with atopic dermatitis, 15 female chronic pain patients diagnosed with fibromyalgia, and 19 female healthy controls. Intensities of itch and pain sensations were rated on a visual analogue scale. RESULTS: As expected, the patient groups had significantly lower tolerance thresholds for the somatosensory stimuli applied than the healthy controls, supporting generalized sensitization. Moreover, patients with chronic itch consistently reported more itch, while patients with chronic pain partly reported more pain in response to analogous somatosensory stimuli than the healthy controls and the other patient group, indicating symptom-specific sensitization. CONCLUSION: The present study provides preliminary support that both generalized and symptom-specific sensitization processes play a role in the regulation and processing of somatosensory stimulation of patients with chronic itch and pain.