# GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats
## 1 Introduction  
According to the IASP, neuropathic pain is defined as a pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. It affects 6.9% to 10% of the general population [1] and patients often experience bothersome symptoms as pain due to non-painful stimulations (allodynia) and an enhanced pain response (hyperalgesia). These symptoms frequently worsen and respond less to pharmacological treatment over time having a negative impact on quality of life [2]. To date, gabapentin, pregabalin, duloxetine, venfalaxine, and some tricyclic antidepressants have the strongest evidence for use and are recommended as first-line treatments for neuropathic pain. However, most of the drugs used are effective in less than 50% of patients and have adverse effects that restricts their medical utility [2, 3]. Thus, other therapeutic options are required for patients.  
Orphan G-protein-coupled receptors (GPCR) represent a diverse family of cell-surface receptors and proteins for which the endogenous ligand and function are unknown. Orphan GPCR are extensively distributed in the nervous system representing one of the most important opportunities to identify better therapeutic targets to manage neuropathic pain [4].  
The orphan receptor GPR55 gene is mapped to human chromosome 2q37 which codes for a protein of 319 amino acids [5]. GPR55 receptors seem to be involved in glucose homeostasis, anti-inflammatory effects and analgesia [6; 7]. In nociceptive neurons of the dorsal root ganglion (DRG), GPR55 receptor is mainly coupled to Gq and G12/13 proteins and its stimulation activates phospholipase C and RhoA GTPase to raise intracellular calcium and to inhibit voltage-gated potassium channels [8; 9]. In the nervous system, GPR55 is localized in several brain regions associated with pain processing, such as the thalamus, periaqueductal gray, hippocampus, frontal cortex, striatum and brainstem, and the spinal cord [5; 10; 11; 12]. In the DRG, it is strongly expressed in medium- to large-diameter neurons, and satellite glial cells [8; 13]. The role of GPR55 in neuropathic pain remains controversial since some evidence indicates that its activation induces nociception [9; 14; 15], whereas other evidence shows a lack of effect [16]. Hence, the role of GPR55 in neuropathic pain processing deserves to be investigated in further experiments.  
The orphan receptor GPR119 has 335 amino acids in length and is coupled to a Gs protein increasing cAMP [17; 18]. This receptor has been understood to be mainly involved in glucose homeostasis and weight loss [6]. In nociception, it is highly expressed in dorsal root ganglia, trigeminal ganglia, spinal cord and some brain areas involved in pain modulation, such as the hypothalamus, hippocampus, medulla and cerebral cortex in the rat [19]. Notwithstanding this, its involvement in pain processing is unknown.  
Based on the above, the current study was performed to evaluate the participation of GPR55 and GPR119 receptors in the processing of neuropathic pain induced by L5-L6 spinal nerve ligation in rats.