The delta opioid receptor tool box

Abstract

In recent years, the delta opioid receptor has attracted Increasing Interest as a target for the treatment of chronic pain and emotional disorders. Due to their therapeutic potential, numerous tools have been developed to study the delta opioid receptor from both a molecular and a functional perspective. This review summarizes the most commonly available tools, with an emphasis on their use and limitations. Here, we describe (1) the cell-based assays used to study the delta opioid receptor. (2) The features of several delta opioid receptor ligands, including peptide and non-peptide drugs. (3) The existing approaches to detect delta opioid receptors in fixed tissue, and debates that surround these techniques. (4) Behavioral assays used to study the in vivo effects of delta opioid receptor agonists; including locomotor stimulation and convulsions that are induced by some ligands, but not others. (5) The characterization of genetically modified mice used specifically to study the delta opioid receptor. Overall, this review aims to provide a guideline for the use of these tools with the final goal of increasing our understanding of delta opioid receptor physiology.

Tolerance to high‐internalizing δ opioid receptor agonist is critically mediated by arrestin 2

“…The complete Freund's adjuvant (CFA)‐induced inflammatory pain model was performed as described previously (Pradhan et al ., ; Vicente‐Sanchez et al ., ). Briefly, inflammation was induced by injecting 13 μL of CFA (Sigma‐Aldrich) into the plantar surface of the hindpaw, and animals were tested 72 h after injection.…”

Emerging Treatment Targets for Migraine and Other Headaches

“…Although δ agonists are not highly effective in acute pain, they have shown efficacy in a number of chronic pain states, including models of inflammatory and neuropathic pain . δ agonists appear to be particularly effective in models of headache .…”

“…This latter finding particularly supports the distinction between the µ and δ receptors, as chronic µ receptor stimulation by morphine resulted in a correlate of mediation overuse headache which could still be blocked by δ receptor activation. Preclinical studies indicate that δ opioid receptors are functionally upregulated during chronic peripheral pain states, and may serve as an endogenous protective mechanism to counteract increased pain signaling. Ongoing studies are underway to determine if this upregulation is also observed in headache models.…”

“…60 Although δ agonists are not highly effective in acute pain, they have shown efficacy in a number of chronic pain states, including models of inflammatory and neuropathic pain. 61 δ agonists appear to be particularly effective in models of headache. 47 In a behavioral model of migraine-associated pain, nitroglycerin, a known human migraine trigger, 62 caused severe mechanical hyperalgesia in mice that was prevented by 3 different δ agonists.…”

SNC80 and naltrindole modulate voltage-dependent sodium, potassium and calcium channels via a putatively delta opioid receptor-independent mechanism

“…Previously, NG108-15 cells have been used as a model for studying of DOR (Roerig et al 1992;Heiss et al 2009) and DORs were cloned for the first time from these cells (Evans et al 1992;Kieffer et al 1992). However, expression of these receptors is very unstable and at higher passage number cells express little or no receptors (Vicente-Sanchez et al 2016).…”