## **Core Concept**
The triple response of Lewis, also known as the triple response of skin, is a physiological response to mild damage of the skin, typically observed after stroking or lightly pricking the skin. This response involves three main reactions: **red line** (or red line of demarcation), **flare**, and **wheal**. The flare response is a critical component of this reaction.

## **Why the Correct Answer is Right**
The **flare** response in the triple response is primarily mediated by **histamine** released from damaged skin cells and **mast cells**. Histamine causes local **vasodilation** and increased permeability. However, the flare is more specifically related to the **axon reflex**, where histamine stimulates the release of **substance P** and **calcitonin gene-related peptide (CGRP)** from sensory nerve endings. These neuropeptides then cause vasodilation of nearby blood vessels, leading to the spreading erythema (flare).

## **Why Each Wrong Option is Incorrect**
- **Option A:** This option is incorrect because, although histamine is involved in the initial steps leading to the flare, the direct mediation of the flare response involves the axon reflex and release of neuropeptides.
- **Option B:** This option might seem plausible due to the involvement of the nervous system in the axon reflex, but it is not directly related to the mediation of the flare response.
- **Option C:** This could potentially refer to another mechanism or substance but is not directly implicated in the mediation of the flare response.

## **Clinical Pearl / High-Yield Fact**
A key point to remember is that the **flare** response is an example of a **neurogenic inflammation**, where the response is mediated by neural reflexes rather than a direct effect of the inflammatory mediator on blood vessels. This is a critical concept in understanding dermatological and neurological interactions.

## **Correct Answer:** B. **Substance P (and CGRP via axon reflex)**