The journal of pain : official journal of the American Pain Society
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The risk of developing chronic pain is twice as high among people with a history of childhood maltreatment compared to those without these experiences. It is unclear, however, whether childhood maltreatment might lead to lower or higher perception of pain. In this paper, we investigate the association between childhood maltreatment and pain sensitivity. ⋯ Individuals reporting childhood sexual abuse, emotional abuse or neglect and physical neglect could on average withstand hot and cold pain of 1.03 °C [0.13, 1.84] to 3.20 °C [0.62, 5.97] more across different types of abuse compared to those with no emotional abuse or (physical) neglect history. Physical abuse was not associated with pain sensitivity. The current findings suggest that childhood maltreatment might lead to habituation to painful stimuli as opposed to increased pain sensitivity.
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Sickle cell disease (SCD) is an inherited hemolytic disorder accompanied by chronic pain and recurrent acute painful episodes known as vaso-occlusive crises (VOCs). Increased Glx (glutamate+glutamine) and lowered GABA concentration have been reported in the insula of patients with fibromyalgia, a nociplastic chronic pain condition, and may affect the pathophysiology of pain-related syndromes. Therefore, proton magnetic resonance spectroscopy (1H-MRS) was conducted to measure levels of Glx and other brain metabolites using a single voxel (size: 2×3×3 cm3) in the right posterior insula cortex (PIC) in 17 individuals with SCD and 17 ethnicity-, age- and sex-matched healthy controls (HCs). ⋯ These results suggest that elevated excitatory neurotransmission in the insula might contribute to nociplastic pain in SCD. PERSPECTIVE: Our work highlighted the innovative finding of elevated levels of the excitatory neurotransmitter glutamate with glutamine in patients with SCD compared to healthy controls. The positive relationship between Glx/tCr and the frequency of VOCs suggests that an excitatory brain neurotransmitter imbalance may be involved in VOCs.
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The concomitant epidemics of chronic pain and opioid misuse in the United States have led to a call for novel analgesics with limited abuse potential. Previously, we have shown that co-delivery of a novel combination targeting both μ- and δ-opioid receptors in the peripheral and central nervous systems can produce synergistic analgesia. Loperamide, a peripherally restricted μ-opioid agonist, and oxymorphindole, a δ-opioid receptor partial agonist, synergize in multiple mouse models of hyperalgesia. ⋯ From these data we conclude that the combination of oxymorphindole and loperamide or the combination of N-benzyl-oxymorphindole and loperamide reverse incisional hyperalgesia, likely by acting in the periphery, in a large animal model without adverse effects on respiration or heart rate. PERSPECTIVE: This article presents novel opioid combinations, the μ-opioid agonist loperamide with a δ-opioid agonist, either oxymorphindole (OMI) or N-benzyl-oxymorphindole (BOMI), that relieve pain in mice and pigs without adverse side effects. These therapies could help clinicians manage pain in patients while reducing overall opioid burden and limiting side effects.
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The study of orofacial neuropathic pain necessitates the use of innovative assessment techniques, such as the facial expression of pain, which mirrors the internal state of the animals and could be utilized to identify the neural correlations involved. The Anterior Cingulate Cortex (ACC) is a crucial center in the processing of sensory and affective components of acute and neuropathic pain. However, its role in the facial response to pain remains a mystery. ⋯ Our study underscores the significant role of ACC in the development of signs of orofacial neuropathic pain, such as exacerbated facial response to mechanical stimuli. PERSPECTIVE: This article presents evidence on the sensory coding of mechanical stimulation in a neuropathic pain model in the Anterior Cingulate Cortex, using facial expression as a manifestation of the internal painful state. This evaluation provides a novel approach to evaluating the well-being of animals with neuropathic pain.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathy that develops in patients treated with certain anticancer drugs. Oxaliplatin (OXA) causes CIPN in approximately 80-90 % of patients; thus, it is necessary to elucidate its underlying mechanism and develop effective treatments and prevention methods. The purpose of this study was to determine whether the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system in the spinal dorsal horn is involved in OXA-induced acute cold allodynia and examine the effect of a PAC1 receptor antagonist. ⋯ PERSPECTIVE: Cold allodynia is a hallmark of OXA-induced peripheral neuropathy. This study demonstrated the involvement of spinal PACAP/PAC1 receptors in OXA-induced acute cold allodynia. We propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of OXA-induced acute cold allodynia.