Table 1.
Functional expression of the NOP receptor in rodent nociceptive system and effects of N/OFQ and NOP receptor agonists in rodent models of acute pain
| NOP receptor expression | Function of N/OFQ and NOP receptor agonists | |||||
|---|---|---|---|---|---|---|
| Region | mRNA | Protein | In vitro | In vivo | ||
| Supraspinal | Thalamus | Many thalamic nuclei [ISH] (Neal et al., 1999a) | Many thalamic nuclei [RLB] (Neal et al., 1999a) | ↓ firing rate of thalamic neurons [in vivo electrophysiology rat] (Albrecht et al., 2001) | i.c.v.: no effect alone, but reduced i.c.v. DAMGO-induced antinociception [tail withdrawal mouse] (Mogil et al., 1996b) | |
| Amygdala | Many amygdaloid nuclei [ISH] (Neal et al., 1999a) | Many amygdaloid nuclei [RLB] (Neal et al., 1999a), [IHC] (Anton et al., 1996) | ↑ GIRK current in CeA neurons [patch clamp] (Meis and Pape, 1998) | m.i.: antinociceptive [tail flick rat] (Shane et al., 2001) | i.c.v.: no effect alone, but reversed systemic and i.c.v. morphine-induced antinociception in rats [tail flick] (Tian et al., 1997a) and mice [tail flick] (King et al., 1998), [tail withdrawal] (Mogil et al., 1996a) | |
| ↓ IPSC in CeA neurons [patch clamp] (Roberto and Siggins, 2006) | ||||||
| ↑ K+ current, hyperpolarized CeA-PAG projection neurons [patch clamp] (Chen et al., 2009) (Chieng and Christie, 2010) | ||||||
| PAG | High expression through entire extent [ISH] (Neal et al., 1999a) | Dense N/OFQ binding [RLB] (Neal et al., 1999a) | ↑ K+ current, ↓ IPSCs and EPSCs [patch clamp] (Vaughan et al., 1997) | m.i.: reduced intra-PAG morphine-induced antinociception [tail flick rat] (Morgan et al., 1997) | i.c.v.: pronociceptive alone, inhibited i.c.v. morphine-induced antinociception [tail withdrawal mouse] (Calo et al., 1998) | |
| ↓ N-, P/Q-type Ca2+ current [patch clamp] (Connor and Christie, 1998) | m.i.: antinociceptive [tail flick rat] (Shane et al., 2003) | i.c.v. N/OFQ(1-13): pronociceptive [tail flick rat] (YQ Wang et al., 1999b) | ||||
| m.i.: pronociceptive [tail flick rat] (Lu et al., 2010) | i.c.v.: pronociceptive [hot plate mouse] (Liu et al., 2006) | |||||
| i.c.v.: pronociceptive [tail flick mouse] (Wang et al., 2006) | ||||||
| RVM | High expression in C1, A1 cell group [ISH] (Neal et al., 1999a) | Moderate N/OFQ binding in C1, A1 cell group [RLB] (Neal et al., 1999a) | ↑ K+ current, ↓ Ca2+ current in primary and secondary RVM neurons [patch clamp] (Vaughan et al., 2001) | m.i.: no effect alone, but reduced intra-RVM DAMGO-induced antinociception [tail flick rat] (Heinricher et al., 1997) | ||
| m.i.: no effect alone, but reduced intra-PAG DAMGO-induced antinociception [tail flick rat] (Pan et al., 2000) | ||||||
| Spinal | Intrinsic neurons | Lamina I, II, X, ventral horn [ISH] (Pettersson et al., 2002) | Dorsal horn [RLB] (Pettersson et al., 2002) | ↓ A- and C-fibre responses [hemisected spinal cord] (Faber et al., 1996) | i.t.: ↓ C-fibre evoked wind-up of DH neurons [in vivo electrophysiology rat] (Stanfa et al., 1996) | |
| Dorsal, ventral horn [ISH] (Mika et al., 2003) | Majority of N/OFQ binding sites spared by rhizotomy (Le Cudennec et al., 2002) | Hyperpolarized lamina II neurons by ↑ K+ conductance [patch clamp] (Lai et al., 1997) | i.t.: antinociceptive, potentiated s.c. morphine-induced antinociception [tail flick rat] (Tian et al., 1997a) | |||
| ↓ glutamate-, kainate-, quisqualate-induced currents in DH neurons [patch clamp] (Shu et al., 1998) | i.t. N/OFQ(1-13): antinociceptive [tail flick rat] (YQ Wang et al., 1999b) | |||||
| ↑ GIRK current in lamina II neurons [patch clamp] (Luo et al., 2001) | i.t. N/OFQ(1-13): antinociceptive [tail flick rat] (YQ Wang et al., 1999b) | |||||
| Proximal PAF (presynaptic) | Rhizotomy reduced N/OFQ binding sites by 18% [RLB] (Le Cudennec et al., 2002) | ↓ Aδ-, C-fibre EPSCs of lamina I and lamina II neurons [patch clamp] (Lai et al., 1997; Liebel et al., 1997; Luo et al., 2002; Murali et al., 2012) | ||||
| Peripheral | DRG neuron (cell body) | Large neurons [ISH] (Pettersson et al., 2002) | Medium and large neurons [RLB] (Pettersson et al., 2002) | ↓ T-type Ca2+ currents in medium-sized neurons [patch clamp] (Abdulla and Smith, 1997) | ||
| Co-localization in majority of SP- and CGRP-positive neurons [ISH, RT-PCR] (Mika et al., 2003) | Small and medium neurons [IHC] (Chen and Sommer, 2006) | ↓ N-type Ca2+ currents (Abdulla and Smith, 1998) in small IB4 negative neurons [patch clamp] (Murali et al., 2012) | ||||
| Distal PAF (dendritic) | Not in skin [ISH] (Pettersson et al., 2002) | s.c. in the tail: antinociceptive [tail flick mouse] (Kolesnikov and Pasternak, 1999) | ||||
| i.pl.: ↓ i.pl. capsaicin-induced nociception in mice (Sakurada et al., 2005) | ||||||
| i.pl. Ro64-6198: no effect on mechanical and thermal nociception [PPT, PWL rat] (Obara et al., 2005) | ||||||
No data are published for fields that are left blank. ↑, activation/increase; ↓, inhibition/decrease; CeA, central nucleus of amygdala; CGRP, calcitonin gene-related peptide; DAMGO, (D-Ala2, N-Me-Phe4, Gly-ol)-enkephalin; DH, dorsal horn; EPSC, excitatory postsynaptic current; GIRK, G–protein-activated inward rectifier K+; IB4, isolectin B4; IHC, immunohistochemistry; IPSC, inhibitory postsynaptic current; ISH, in situ hybridization; m.i., microinjected; PAF, primary afferent fibre; PPT, paw pressure test; PWL, paw withdrawal latency; RLB, radioligand binding; Ro64-6198, selective NOP receptor agonist; SP, substance P.