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Pain is a common symptom among patients with cancer. Adequate pain assessment and management are critical to improve the quality of life and health outcomes in this population. In this review, the authors provide a framework for safely and effectively managing cancer-related pain by summarizing the evidence for the importance of controlling pain, the barriers to adequate pain management, strategies to assess and manage cancer-related pain, how to manage pain in patients at risk of substance use disorder, and considerations when managing pain in a survivorship population. CA Cancer J Clin 2018;68:182-196. © 2018 American Cancer Society.

Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve–induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus–VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism–based therapeutic strategy for the anxiodepressive consequences of neuropathic pain., Activating excitatory neurons or inhibiting GABAergice neurons of the VLO improved anxiodepressive consequences of neuropathic pain in a trigeminal neuralgia mouse model.

The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway to the spinal cord relaying in the periaqueductal gray (PAG). This study examines whether activation of D(1)-like and D(2)-like dopamine receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO, D(2)-like dopamine receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the D(2)-like (D(2)/D(3)) dopamine receptor agonist quinpirole (0.1-2.0 microg), but not D(1)-like (D(1)/D(5)) receptor agonist SKF-38393 (1.0, 5.0 microg), into VLO produced dose-dependent antinociception which was antagonized by the D(2)-like (D(2)/D(3)) receptor antagonist raclopride (1.5 microg). We also found that VLO application of the GABA(A) receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the quinpirole-induced inhibition of the TF reflex, whereas the GABA(A) receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the quinpirole-induced inhibition. These results suggest that D(2)-like, but not D(1)-like, dopamine receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the D(2)-like receptor mediated effect. These findings provide support for the hypothesis that D(2)-like receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal dorsal horn.