**3.5 TRP channels**

The physiological mechanisms of pain and temperature stimuli indicate the transient receptor potential (TRP) as a target in this regard [110]. The TRP channels superfamily is constituted of transmembrane cationic ionotropic receptors. In mammals, six subfamilies classify the TRP channels into two groups. The first group: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), and TRPM (melastatin). The second group is composed of TRPML (mucolipin) and TRPP (polycystic). This chapter will discuss the most addressed subfamilies in the scientific literature: TRPV, TRPM, and TRPA based on their involvement in inflammation and pain. These subfamilies are classified in TRPV1–6, TRPM1–8, and TRPA1 receptors [111, 112].

#### **Figure 3.**

*IL-1*β *and IL-18 synthesis after P2X7R activation. The first signaling occurs with the ProIL-1*β *and ProIL-18 transcription after TLRs receptor activation (TLR4). The second signal arrives with the eATP stimulating the P2X7R. The receptor activation induces the NLRP3 inflammasome complex, and finally, IL-1*β *and IL-18 conversion for mature form.*


*Inflammatory Mediators Leading to Edema Formation through Plasma Membrane Receptors DOI: http://dx.doi.org/10.5772/intechopen.99230*

#### **Table 4.**

*Purinergic receptors.*

TRPV1 is the most studied TRP channel because of its noxious heat and inflammation perception. TRPV1 is a pore-forming protein, like P2X7R and other TRPs, such as TRPV2–4, TRPA1, and TRPM8 (**Table 5**). All these channels promote pore opening, and molecules flux up to 900 Da [117]. Capsaicin is one TRPV1 receptor agonist and plays a critical role in nociception pathogenesis [124].

The TRPV1 receptor (heat sensor) together with TRPA1 (cold sensor) can modulate the neuropeptide molecules release like substance P. This molecule encompasses many biochemical processes involved in inflammation, such as histamine and serotonin released by mast cells, which leads to increased vascular permeability and hyperalgesia [113]. Hoffmeister and co-authors [125] described a reversion in edema and pain caused by monosodium urate crystals after TRPV1 inhibition. These findings may be associated with the mechanism mentioned above with TRPV1 participation. Additionally, TRPV1 and TRPA1 receptor inhibition


#### **Table 5.**

*Transient receptors potential.*

decreased pro-inflammatory cytokines levels, such as TNF-α, IL-1β, and IL-6 in an endotoxin-induced lung injury model [114]. Interestingly, Li et al. [115] demonstrated TRPV1 activation associated with NF-kβ phosphorylation through the intracellular Ca2+ influx. Based on this data, TRPV1 receptors play a critical role in the modulation of the pro-inflammatory cytokines.

Another notorious receptor involved in the low temperatures detection in conjunction with TRPA1 is the TRPM8 receptor. TRPM8 exhibits an essential role in neuropathic pain and anti-inflammatory effects [111]. TRPM8 is the most studied receptor in cold physiology. TRPM8 activation reverses the hyperalgesia caused by TRPV1 and TRPA1 stimuli [16]. Experiments using eucalyptol, a TRPM8 agonist, show promising results in reducing pro-inflammatory cytokines in paw edema [121]. Studies with cold therapy can have analgesic and anti-edema effects [122]. These findings make the TRPM8 receptor a target in this context.

*Inflammatory Mediators Leading to Edema Formation through Plasma Membrane Receptors DOI: http://dx.doi.org/10.5772/intechopen.99230*
