Merkel cells and touch domes: more than mechanosensory functions?

The touch dome (TD) is an innervated structure in the epidermis of mammalian skin. Composed of specialized keratinocytes and neuroendocrine Merkel cells, the TD has distinct molecular characteristics compared to the surrounding epidermal keratinocytes. Much of the research on Merkel cell function has focused on their role in mechanosensation, specifically light touch. Recently, more has been discovered about Merkel cell molecular characteristics and their cells of origin. Here we review Merkel cell and TD biology, and discuss potential functions beyond mechanosensation.

Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model.

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

Inflammation-induced changes in rostral ventromedial medulla mu and kappa opioid receptor mediated antinociception.

Acute microinjection of mu-, delta-, or kappa-opioid receptor (MOPr, DOPr, KOPr) agonists into the rostral ventromedial medulla (RVM) produces antinociception. Thermal antinociception produced by MOPr and DOPr agonists is potentiated during inflammation [Hurley RW, Hammond DL. The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 2000;20:1249-59]. Whether this potentiation extends to other stimulus modalities or to KOPr agonists is unknown. To examine these issues, rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA). Antinociception produced by RVM infusion of the KOPr agonist, U69593, and the MOPr agonist, DAMGO, was tested 4h-2 weeks thereafter. Thermal paw withdrawal latencies (PWLs) were assessed using the Hargreaves method. Mechanical thresholds were determined with the Von Frey and Randall-Selitto method. PWLs of the inflamed paw were reduced 4h-2 weeks after CFA injection. Infusion of either U69593 or DAMGO increased PWLs in CFA treated rats. A bilateral enhancement of the response to both agonists was observed 2 weeks relative to 4h post-CFA injection. Mechanical thresholds of the inflamed paw were decreased for >2 weeks post-CFA injection. Infusion of either agonist elevated thresholds of the inflamed and non-inflamed paws of CFA-treated rats. The magnitude of these effects was greater 2 weeks post-CFA injection for DAMGO and increased progressively for U69593. These data demonstrate that RVM infusion of MOPr or KOPr agonists attenuates CFA-evoked thermal and tactile allodynia and that these effects increase during prolonged inflammation. The augmented response of the non-inflamed paw to agonists suggests that inflammation induces centrally-mediated neuroplastic changes which enhance MOPr- and KOPr-mediated antinociception.

A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.

The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement without altering baseline nociceptive threshold. Similarly, in TRPV4(-/-) knock-out mice, inflammatory soup failed to induce any significant mechanical or osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators engage the TRPV4-mediated mechanism of sensitization by direct action on dissociated primary afferent neurons. Additional behavioral observations suggested that multiple mediators are necessary to achieve sufficient activation of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In addition, direct activation of protein kinase A or protein kinase C epsilon, two pathways that mediate inflammation-induced mechanical hyperalgesia, also induced hyperalgesia for both hypotonic and mechanical stimuli that was decreased by TRPV4 antisense and absent in TRPV4(-/-) mice. We conclude that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues.

Objective measurement of allergic reactions in the eye.

PURPOSE OF REVIEW: Conjunctival allergen challenge has become a useful model of human ocular allergy and an accepted method for studying the effects of topical antiinflammatory medications. Conjunctival allergen challenge reactions are typically evaluated in a subjective fashion. Erythema and edema are graded by observation, using a 0 to 4 scale. Itching is graded on a 0 to 4 scale by questioning the subject. We have reviewed the recent literature on conjunctival allergen challenge, including recently developed methods aimed at objective assessment of ocular allergic reactions, such as the erythema, edema, sensation, or EES, method. RECENT FINDINGS: Conjunctival erythema can be measured objectively using a spectroradiometer, or colorimeter, a device which measures the chromaticity of reflected light, and provides the x, or u', and y, or v', coordinates of any color. Edema of the eyelids and conjunctiva can be measured using a fractional millimeter reticule in the eyepiece of a slit lamp microscope. Ocular surface sensation can be evaluated using the aesthesiometer of Cochet and Bonnet, or by using a 'sensation index', a measurement that takes into account the intensity and duration of itching. SUMMARY: CAC reactions can be measured objectively using the erythema, edema, sensation method, as well as subjectively by observation and questioning.

El tacto, un sentido muy especial / Tacto, a very special felt

El autor destaca la importancia de la experiencia táctil como estímulo del desarrollo y la adaptación social del ser humano, a partir de la vida intrauterina. Subraya la influencia del contacto con otro ser humano y diferencia sus afectos positivos o negativos en función de la sensibilidad del niño en etapas muy tempranas (AU)

El tacto, un sentido muy especial / Tacto, a very special felt

El autor destaca la importancia de la experiencia táctil como estímulo del desarrollo y la adaptación social del ser humano, a partir de la vida intrauterina. Subraya la influencia del contacto con otro ser humano y diferencia sus afectos positivos o negativos en función de la sensibilidad del niño en etapas muy tempranas

Psychoimmunologic effects of therapeutic touch on practitioners and recently bereaved recipients: a pilot study.

The purposes of this descriptive pilot study were to address conceptual inconsistencies and several other methodologic problems identified in previous Therapeutic Touch (TT) research, while also providing direction for future TT studies by attempting to determine the appropriateness and suitability of a combination of psychologic and immunologic measures in the ongoing empiric evaluation of TT. Research questions were derived from a unitary perspective. Data on both practitioners and recipients were collected and examined for patterns and relationships. Changes that may be related to TT were observed in immunologic, psychologic, and unitary measures. Directions for future research within a unitary framework were postulated.