Topical acetylsalicylate attenuates capsaicin induced pain, flare and allodynia but not thermal hyperalgesia

doi:10.1016/0304-3940(96)12868-8

Neuroscience Letters

Volume 214, Issue 1, 16 August 1996, Pages 72-74

https://doi.org/10.1016/0304-3940(96)12868-8 Get rights and content

Abstract

The effect of acetylsalicylic acid (ASA) on capsaicin-evoked activation of cutaneous nociceptors was tested in a double blind study in 10 volunteers. Capsaicin (2% in ethanol) was applied topically for 30 min. Topical ASA (0.25 g/ml) reduced pain intensity and axon reflex flare size. Also, areas of secondary hyperalgesia to light touch and pin-prick were diminished. In contrast, capsaicin-induced heat hyperalgesia was unaffected by ASA. It is concluded that ASA counteracts the excitatory effects of capsaicin on nociceptors and mechanical hyperalgesia but not its sensitizing action to heat.

References (20)

P.W. Beck et al.
Nervous outflow from the cat's foot during noxious radiant heat stimulation
Brain Res.
(1974)
S. Bevan et al.
Protons: small stimulants of capsaicinsensitive sensory nerves
Trends Neurosci.
(1994)
S. Kilo et al.
Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man
Pain
(1995)
M. Koltzenburg et al.
Dynamic and static components of mechanical hyperalgesia in human hairy skin
Pain
(1992)
M. Petersen et al.
Effect of protons on the inward current evoked by capsaicin in isolated dorsal root ganglion cells
Pain
(1993)
D.A. Simone et al.
Early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilatation in humans
Pain
(1991)
K.H. Steen et al.
Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin
Pain
(1995)
A. Szallasi et al.
Protein inhibition of (H 3) resiniferatoxin binding to vanilloid (capsaicin) receptors in rat spinal cord
Eur. J. Pharmacol. Mol. Pharmacol.
(1995)
T.K. Baumann et al.
Neurogenic hyperalgesia the search for the primary cutaneous afferent fibers that contribute to capsaicin induced pain and hyperalgesia
J. Neurophysiol.
(1991)
B. Diehl et al.
The influence of mechanical stimuli and of acetylsalicylic acid on the discharges of slowly conducting afferent units from normal and inflamed muscle in the rat
Exp. Brain Res.
(1993)

There are more references available in the full text version of this article.

Cited by (37)

Topical high-concentration (40%) menthol - Somatosensory profile of a human surrogate pain model
2011, Journal of Pain
Citation Excerpt :
This study demonstrates that menthol is a suitable model for cold and pinprick hyperalgesia and for the first time that cold hyperalgesia has to be acknowledged to be an unstable and pinprick hyperalgesia to be a stable phenomenon within 4 hours after application. This knowledge has to be taken into account when performing psychophysical and pharmacological interventions using the menthol pain model as it has been extensively performed in the capsaicin and heat/capsaicin model2,14,16,22,39,40,42,46,47,54-58 and a first study in the menthol model.1 Again, a similar course has been demonstrated after intradermal capsaicin injection and in the heat/capsaicin model.27,48,49
Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain. Topical application of menthol has been proposed as model to study cold hyperalgesia. The aim of this psychophysical study was to characterize the human surrogate of neuropathic pain of topical menthol application by using a standardized and validated protocol of quantitative sensory testing (QST). Additionally, we assessed the course of the signs elicited by menthol application over time. High-concentration 40% L-menthol was applied topically on hairy skin in 12 healthy subjects. Standardized psychophysical tests (QST) assessing 13 parameters including thermal and mechanical detection and pain thresholds were obtained before and every 45 minutes after menthol removal up to 4 hours after menthol application. Menthol decreased the cold pain threshold, mechanical pain threshold, and increased the mechanical pain sensitivity in all subjects displaying cold and mechanical pinprick hyperalgesia. In all subjects, an area of secondary pinprick hyperalgesia could be determined. Within the observation time, the decreased cold pain threshold increased continuously, whereas the signs of primary and secondary pinprick hyperalgesia remained stable. The data suggest that topical 40% menthol application is a useful model for studies of cold hyperalgesia and pinprick hyperalgesia in humans.
This study establishes the topical application of high-concentration 40% menthol as a useful stable model for studies of cold hyperalgesia and pinprick hyperalgesia in humans. The provided long-term data are important for psychophysical and pharmacological research in humans and provide us with insights on experimental cold and mechanical hyperalgesia.
Topical application of compound ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation
2011, Journal of Pain
Citation Excerpt :
Therefore, CIC treatment may inhibit multiple aspects of inflammatory responses in addition to inhibiting the sensory neuron excitability, the sodium channel expression and activity of NF-κB, expression of COX-2, and the cytokine IL-1β in the inflamed ganglion. Several lines of studies have compared topical ibuprofen gel and oral ibuprofen in clinical experimental pain paradigms and concluded that topical application of NSAIDs produces analgesia in models of cutaneous pain24,33,34 and muscle pain.33,47 In a clinical context, several reviews have all concluded that there was clear evidence to support efficacy of topical NSAIDs given by gel, spray, or patch for conditions of soft-tissue injuries (eg, sprains, strains, tendonitis) and rheumatic diseases,14,26,33,50,54 and for sports-related soft-tissue injury.10
There is lack of evidence that topical application of an anti-inflammatory reagent could reduce pain due to intervertebral foramen (IVF) inflammation (IVFI). We investigated analgesic effects and underlying mechanisms of topical application of a compound ibuprofen cream (CIC) onto the surface of back skin covering the inflamed L₅ IVF in a rat model. Repetitive CIC treatment (∼.54 g each treatment daily for 5 consecutive days) significantly reduces severity and duration of IVFI-induced thermal hyperalgesia and mechanical allodynia by 80 to 100% and 50 to 66%, respectively. Electrophysiological studies and Western blot analysis demonstrated that CIC treatment significantly inhibited hyperexcitability of the inflamed dorsal root ganglion (DRG) neurons and upregulation of Nav1.7 and Nav1.8 protein, respectively. Pathological manifestations of the inflamed DRG were also markedly improved following CIC treatment. Further, in the inflamed DRGs, phosphorylation and expression of transcription factor NF-κB and pro-inflammatory enzyme cyclooxygenase-2 (COX-2) were significantly increased, while a cytokine IL-1β level was increased. IVFI-induced upregulation of these molecules was significantly inhibited by CIC treatment. This study provides evidence that an anti-inflammatory reagent can be used topically to suppress pain due to IVFI and/or DRG inflammation through inhibition of sensory neuron hyperexcitability and the immune and inflammatory responses.
This study suggests a convenient and safe clinical intervention for treating pain due to intervertebral foramen inflammation and similar syndromes.
Topical Analgesics
2009, Perioperative Nursing Clinics
Citation Excerpt :
When NSAIDs are applied topically, bioavailability and plasma concentrations are 5% to 15% of those achieved by systemic delivery.4 In human experimental pain models, topically applied NSAIDs produce analgesia in models of cutaneous pain,5–8 and muscle pain.9 In terms of clinical use, three major reviews—one examining use in musculoskeletal and soft tissue pain,10 another looking at data accrued in over 10,000 patients in 86 trials,11 and the last looking primarily at chronic rheumatic disease4—concluded that there was clear and significant evidence that topical NSAIDs have pain-relieving properties.
Topical analgesic agents
2009, Current Therapy in Pain
Topical Analgesics
2007, Anesthesiology Clinics
Citation Excerpt :
When NSAIDs are applied topically, bioavailability and plasma concentrations are 5% to 15% of those achieved by systemic delivery [4]. In human experimental pain models, topically applied NSAIDs produce analgesia in models of cutaneous pain [5–8] and muscle pain [9]. In terms of clinical use, three major reviews—one examining use in musculoskeletal and soft tissue pain [10], another looking at data accrued in over 10,000 patients in 86 trials [11], and the last looking primarily at chronic rheumatic disease [4]—concluded that there was clear and significant evidence that topical NSAIDs have pain-relieving properties.
Historically, analgesics were applied by the topical route of administration. With the advent of oral formulations of drugs, topical application became less popular among physicians, although patients still rated this method of drug delivery as efficacious and practical. We now appreciate that peripheral mechanisms of actions of a variety of preparations rationalizes their topical application and gives further opportunity to target peripheral receptors and neural pathways that previously required systemic administration to achieve therapeutic effect. Therefore, a peripheral effect can be generated by using locally applied drug and, consequently, systemic concentrations of that drug may not reach the level at which systemic side effects can occur.
Mechanisms of adrenosensitivity in capsaicin induced hyperalgesia
2007, European Journal of Pain
Citation Excerpt :
This discrepancy may be explained by the fact that afferents are directly activated and sensitized via the binding of capsaicin at the TPRV1 receptor (Catarina et al., 2000; Simone et al., 1991). In high tissue concentrations which can be achieved by topical application ASA might directly interact with the TPRV 1 receptor and thereby reduce the signs of capsaicin induced nociceptor activation (Schmelz and Kress, 1996). Transcutaneous iontophoresis of norepinephrine and drugs that release neural stores of norepinephrine (e.g. tyramine) exacerbate thermal hyperalgesia in skin made sensitive to heat by the topical application of capsaicin.
It is well known that iontophoresis of norepinephrine in capsaicin treated skin is followed by an increase in thermal hyperalgesia. It is unclear if this action on nocicepitive afferents involves the release of prostaglandins. The aim of the present study was to determine: (1) the effect of norepinephrine iontophoresis on spontaneous and evoked pain in the human skin after topical application of capsaicin; (2) the effect of cyclooxygenase (COX) inhibition on changes in pain perception induced by norepinephrine application.
Ten volunteers were included in the study. Iontophoresis of norepinephrine or saline was performed in a randomized cross over design on the volar aspect of the forearm after topical application of capsaicin. In the second part of the study single iv. injections of saline or acetylsalicylic acid were performed in a randomized double blind cross over design. After the injection norepinephrine iontophoresis was performed on the skin treated with topical capsaicin. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured before and after each iontophoresis.
Norepinephrine did enhance spontaneous pain and mechanical and thermal hyperalgesia in capsaicin treated skin. Inhibition of COX I and II had no effect on the norepinephrine induced changes in pain perception.
The results do not support the assumption that in human skin sensitized by topical capsaicin application of norepinephrine acts on nociceptive afferents via the release of prostaglandins. Thus, a direct action of norepinephrine on adrenergic receptors in the membrane of the afferent fibers is most likely.

View all citing articles on Scopus

^☆: This work was supported by the Deutsche Forschungsgemeinschaft, SFB 353.

View full text

Topical acetylsalicylate attenuates capsaicin induced pain, flare and allodynia but not thermal hyperalgesia☆

Abstract

Brain Res.

Trends Neurosci.

Pain

Pain

Pain

Pain

Pain

Eur. J. Pharmacol. Mol. Pharmacol.

Neurogenic hyperalgesia the search for the primary cutaneous afferent fibers that contribute to capsaicin induced pain and hyperalgesia

J. Neurophysiol.

The influence of mechanical stimuli and of acetylsalicylic acid on the discharges of slowly conducting afferent units from normal and inflamed muscle in the rat

Exp. Brain Res.