Cutaneous Wounds Produced by Capsaicin Treatment of Newborn Rats Are Due to Trophic Disturbances

doi:10.1016/S0892-0362(97)00077-9

Neurotoxicology and Teratology

Volume 20, Issue 1, January–February 1998, Pages 75-81

https://doi.org/10.1016/S0892-0362(97)00077-9 Get rights and content

Abstract

The purpose of this study was to show that the occurrence of skin ulcers observed in animals neonatally treated with the neurotoxin capsaicin coincide with trophic disturbances. In addition, cutaneous lesions increased when self-grooming and scratching behaviors reached maturity. The temporal course of cephalic cutaneous wounds in neonatally capsaicin-treated rats was evaluated in animals wearing and not wearing plastic collars from postnatal day (P) 21 until P45. The collars were used to prevent self-grooming and scratching. Beginning on P21, capsaicin-treated rats under both conditions showed transient skin ulcers distributed throughout the head and neck regions. In the capsaicin-treated group without collars, lesions reached their greatest severity by P40, when self-grooming and scratching behaviors obtained adult characteristics. Furthermore, no lesions were detected after 25 days. In the capsaicin-treated rats that wore plastic collars, the widest distribution of skin lesions occurred on P55, after which time lesions vanished detection by 25 days. In this latter group, the cutaneous lesions were exacerbated when collars were removed. Data suggest that transient cutaneous wounds associated with neonatal capsaicin administration may be mediated via capsaicin-sensitive sensory neurons that are involved in trophic and regenerating neural mechanisms.

Section snippets

Animals

Virgin female Wistar strain rats (Rattus norvegicus) (250–300 g) were selectively mated to produce six consecutive litters. Prior to parturition and throughout lactation, dams were housed individually in Plexiglas maternity cages (50 × 40 × 20 cm) containing nesting material (wood shavings). Animals were kept in a colony room at 23 ± 1°C, 50% humidity, and a 12-h illumination cycle (lights on at 0900 h). Food (Purina chow) and water were available ad lib. At birth (P0), 24 pups of both sexes

Results

Body weight comparisons throughout the study yielded no significant differences between control and experimental groups. No statistical differences were observed for pinna detachment (control 15.4 ± 0.1 vs. cap-treated 15.2 ± 0.2) or eye opening (control 14.7 ± 0.1 vs. cap-treated 13.9 ± 0.1 ) (mean ± SE).

Daily inspection of control animals, reared with or without collars, revealed no skin abnormalities. In contrast, Cap-treated animals reared with or without collars showed consistent skin

Discussion

These data indicate that neonatally Cap-treated rats exhibit trophic disturbances that resulted in transient skin lesions. The fact that skin lesions did not appear before P21 in both CAP and CAP + Pc rats suggests the existence of a protective period for pups to the deleterious Cap neurotoxic effects. In this context, it is known that both glabrous and hairy skin in the preweaning rat undergo an intense phase of growth during this time [40]. The thin epidermis, hair follicles, sebaceous

Acknowledgements

This research was supported by doctoral fellowship from CONACyT to PCC-92264, and Grant FOMES (95)-UAT-MMG. The English version of the manuscript was initially corrected by Isabel Pérez Monfort. The final version of the manuscript was corrected by the Neurotoxicology and Teratology editorial assistant office.

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Cited by (14)

Chronically relapsing pruritic dermatitis in the rats treated as neonate with capsaicin; a potential rat model of human atopic dermatitis
2012, Journal of Dermatological Science
Citation Excerpt :
It has been speculated that dysfunction in the nervous system, due to the ablation of capsaicin-sensitive nerve fibers, might be related to the induction of pruritus and scratches, leading to the transient cutaneous lesions [3,4]. However, it is interesting that even in rats wearing a plastic collar to protect themselves from scratching-induced damage, cutaneous lesions were still readily detectable [4], indicating that the scratch itself may not be critical in the manifestation of cutaneous lesion in these rat. Considering recent evidence that the pathogenesis of chronic pruritus involves various resident cells of the skin [5], it is possible that chronic pruritic cutaneous lesion seen in the rats treated with capsaicin is not a simple neurologic disorder but rather a more complicated skin disease associated with dermatological as well as neurological problems.
The pathophysiological mechanisms underlying chronic pruritic skin diseases, e.g. atopic dermatitis (AD), and effective therapies remain elusive due to the paucity of animal models. Recently, we rediscovered that injection of capsaicin into rat pups resulted in vigorous scratching behavior and chronically relapsing AD-like cutaneous lesions well into adulthood.
To characterize the chronic pruritic dermatitis induced by neonatal capsaicin treatment.
Capsaicin (50 mg/kg) was given to rat pups subcutaneously within 48 h after birth, and then scratching behavior, dermatitis and pathophysiological changes of rat skin were investigated chronologically.
Neonatal capsaicin treatment led to not only severe scratching and cutaneous lesions but also a large number of pathophysiological changes in the skin, such as histopathological changes including the deficiency of epidermal filaggrin expression, increases in the number of mast cells, levels of tissue NGF and Th2 cytokine mRNA, impaired skin barrier function and colonization with S. aureus. In addition, we observed the hyperproduction of serum IgE, which is clinically similar to the pathophysiology seen in the patients with atopic dermatitis. During the follow-up observation, the rats showed the alternative periods of relapsing and remitting skin lesions.
Injection of capsaicin into rat pups results in chronically relapsing pruritic dermatitis, similar to human AD. Therefore, we think neonatal capsaicin treatment could be a useful model for studying human AD and for the development of novel therapeutic drugs.
Sensory Nerves as Modulators of Cutaneous Inflammatory Reactions in Health and Disease
2009, NeuroImmune Biology
Citation Excerpt :
These studies indicated that the effect of topical application of capsaicin in inhibiting nociceptive functions is transient; recovery of the nociceptive afferent and the local regulatory, efferent functions of sensory nerve endings occurs within a few days or weeks after cessation of the treatment [55,159,258,260,262,263]. Importantly, trophic lesions of the skin, which may occur after neonatal capsaicin treatment in rats [38,235,264,265], were not observed after topical capsaicin neither in animal [259,260] nor in the human skin [55,159,160,258,263]. Based on these findings, capsaicin-containing creams and ointments have become widely used in a number of pathological conditions associated with pain and inflammation.
Chemosensitive afferent nerves expressing the capsaicin/TRPV1 (transient receptor potential vanilloid receptor-1) receptor are not only involved in the transmission of nociceptive impulses toward the central nervous system, but also play pivotal roles in the initiation and modulation of vascular, inflammatory, and immune reactions in a variety of organs, including the skin. These sensory nerves exert their efferent/local regulatory functions primarily via the release of vasoactive neuropeptides such as calcitonin gene-related peptide and substance P from their terminals upon antidromic or orthodromic stimulation. The chemical changes induced in the neural microenvironment by tissue injury or inflammation may promote the release of proinflammatory sensory neuropeptides and lead to augmentation of the inflammatory response. In turn, the release of anti-inflammatory peptides from sensory nerves or from inflammatory cells may result in an inhibition of cutaneous vascular reactions. The available experimental evidence implicates capsaicin-sensitive sensory nerves in the pathogenesis of certain skin diseases and maladies with cutaneous manifestations. The development of potent nonpeptide antagonists of sensory neuropeptides, the capsaicin/TRPV1 receptor, and the proteinase-activated receptors may offer new possibilities for the management of certain skin diseases and the itch and pain associated with altered sensory nerve functions.
Delta opioid receptor activation modulates affective pain and modality-specific pain hypersensitivity associated with chronic neuropathic pain
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Capsaicin induces atopic dermatitis-like manifestations through dysregulation of proteolytic system and alteration of filaggrin processing in rats
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TRP channels in skin: From physiological implications to clinical significances
2015, Biophysics (Japan)
Distinct reactivity of transient receptor potential vanilloid subtype 1 in a murine model of atopic dermatitis with serious scratching
2014, Open Allergy Journal

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ArticlesCutaneous Wounds Produced by Capsaicin Treatment of Newborn Rats Are Due to Trophic Disturbances

Abstract

Section snippets

Animals

Results

Discussion

Acknowledgements

J. Neurosci. Methods

J. Nutr.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Physiol. Behav.

Neurosci. Lett.

J. Invest. Dermatol.

Neurosci. Lett.

Neuroscience

Physiol. Behav.

Neuroscience

Brain Res. Bull.

Neurosci. Lett.

Brain Res.

Brain Res.

Trophic factors and neuronal survival

Neuron

Interaction between the tachykinins and calcitonin gene-related peptide lead to the modulation of edema formation and blood flow in the rat skin

Br. J. Pharmacol.

The neuropharmacology of capsaicin-review of some recent observations

Pharmacol. Rev.

The effects of substance P on histamine and 5-HT release in the rat

J. Physiol. (Lond.)

Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs

Neuroscience

Effect of capsaicin pretreatment on capsaicin-evoked release immunoreactive somatostatin and substance P from primary sensory neurons

Naunyn Schmiedebergs Arch. Pharmacol.

Differential effects of capsaicin on the content of somatostatin, substance P and neurotensin in the nervous system of the rat

Naunyn Schmiedebergs Arch. Pharmacol.

Articles
Cutaneous Wounds Produced by Capsaicin Treatment of Newborn Rats Are Due to Trophic Disturbances