Jiaci

Neuropathic Pain/Itch in Allergic Conjunctivitis

J Investig Allergol Clin Immunol 2019; Vol. 29(5): 349-356

doi: 10.18176/jiaci.0320

by capsaicin in the nasal mucosa was responsible for this

therapeutic effect. Several trials of topical capsaicin in patients

with nonallergic rhinitis have demonstrated relief of symptoms

and nasal hyperreactivity [51-53].

Systemic neuromodulating agents may constitute another

approach to the management of neuropathic symptoms in

allergic disease. With the recognition that chronic cough is

similar to other hypersensitivity neuropathic syndromes such

as chronic pain [54], gabapentin, a common treatment for

neuropathic pain, has proven clearly efficacious for refractory

cough [55]. The clinical relevance of neuroinflammation

and sensitization has also been extrapolated to chronic

itch. Cevikbas et al [56] described a synergistic role for

γ-aminobutyric acidAand B agonists for addressing symptoms

of itching in murine atopic dermatitis. The utility of gabapentin

has also been demonstrated in this setting [57].

The Table summarizes trials examining neuromodulation

to date for allergic and nonallergic upper airway diseases

presumed to be related to neuroplasticity.

Future Directions

Despite substantial advances in our understanding of the

pathophysiology ofAC, the exact association between targeted

therapy and successful responses remains controversial and

prevents these findings being applied in clinical practice.

However, targeting neuronal inflammation remains a potential

novel strategy for the treatment of AC. The definition of these

pain-relevant neural circuits may facilitate future development

of targeted therapies.

Conclusions

Among the constellation of symptoms that characterizes

AC, many, such as burning and stinging, can be attributed to

chronic neuropathic pain. There is evidence to support that these

hallmark symptoms might be linked to the effects of allergen-

induced neuromodulation. Thus, neurogenic mechanisms may

have a significant role in chronic ocular surface inflammation.

Current management goals in allergic conjunctivitis aim to

minimize the inflammatory cascade associated with allergic

response in the early stages of the pathogenic mechanism.

Based on the mechanistic data reviewed herein, the recognition

that neuronal inflammation explains many of the symptoms in

AC opens new frontiers for drug discovery.

Funding

The authors declare that no funding was received for the

present study.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

1. Undem BJ, Taylor-Clark T. Mechanisms underlying the

neuronal-based symptoms of allergy. J Allergy Clin Immunol.

2014;133(6):1521-34.

2. Gomes PJ.Trends in prevalence and treatment of ocular allergy.

Curr Opin Allergy Clin Immunol. 2014;14(5):451-6.

Table.

Randomized Controlled Trials of Neuropathic Therapies for Allergic/Nonallergic Airway Inflammation

Drug

Mechanism Disease Evaluated

Outcome Assessed

Efficacy

SB-705498

Intranasal TRPV1

Allergic

Total nasal symptom score

No differences in allergen-induced

antagonist

rhinitis

(TNSS) - SB-705498 versus

mean TNSS between SB-705498

placebo, fluticasone

alone and placebo or between

propionate (FP),

SB-705498 plus FP and FP

and SB-705498 + FP

alone [49]

SB-705498

Intranasal TRPV1

Nonallergic

Total symptom score (TSS),

No differences in or maximum

antagonist

rhinitis

expressed as weighted mean

TSS at 1 hour and 24 hours

over 60 minutes (WM0-60)

postdosing on days 1 or 14,

or maximum TSS at 1 hour and

relative to placebo [50]

24 hours postdosing

Capsaicin

Intranasal TRPV1

Idiopathic

Visual analog scale (VAS) and

Significant decrease in VAS

agonist that ablates

rhinitis

therapeutic response evaluation (TRE)

and TRE scores, and abrogation

the TRPV1-SP

scores, and nasal hyperreactivity by means

of nasal hyperreactivity

signaling pathway

of cold dry air (CDA) provocation

to CDA [19]

Capsaicin

Intranasal TRPV1

Nonallergic

Visual analog scale (VAS) scores,

Significant decrease in VAS scores,

agonist that ablates

rhinitis

and nasal hyperreactivity

and abrogation of nasal

the TRPV1-SP

by means of CDA provocation

hyperreactivity to CDA up

signaling pathway

to 9 months after treatment [53]

ICX72

Intranasal TRPV1

Nonallergic Total nasal symptom scores (TNSS),

Significant improvements in TNSS

(capsicum + agonist that ablates

rhinitis

individual symptom scores (ISS)

and each ISS, and average time to

eucalyptol)

the TRPV1-SP

over 2 weeks and average time

first relief of 52.6 seconds [51]

signaling pathway

to first relief

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