A prospective randomized comparative trial of da Vinci SP versus da Vinci Xi in colon and rectosigmoid cancer surgery: a single-center, open-label study protocol.

Spinal cord injury (SCI) is a devastating condition of the central nervous system (CNS) that can lead to long-term disability, significantly impacting both physical and mental health. The burden of SCI predominantly affects the working-age population (aged 20–69), underscoring its substantial implications for global public health []. Neuropathic pain (NP) is a significant issue for many patients with SCI and is a type of pain resulting from damage to or the dysfunction of the nervous system, often described as a tingling, burning, numbness, or electric shock-like sensation [, ]. NP is generally long-lasting and difficult to fully relieve []. NP is an intractable complication following SCI [, ], with prevalence rates ranging from approximately 30% to 80%, and its mechanisms involve complex interactions between the central and peripheral nervous systems []. Depression is a common psychological disorder following SCI and is characterized by a range of symptoms, including low mood, loss of interest, cognitive decline, fatigue, and sleep disturbances []. Neural injury can lead to heightened sensitivity to sensations at the time of injury, and behavioural symptoms akin to depression become more apparent only after prolonged pain [–]. Chronic pain and depression are two of the most common and prevalent nonfatal conditions in clinical practice, and as NP progresses, they often manifest concurrently [, ]. NP may lead to changes in brain structure and function, such as alterations in the prefrontal cortex and limbic system, which are associated with the onset of depression [, ]. The long-term experience of pain can provoke physiological and psychological stress responses, increasing the prevalence of depression. Both conditions may share certain common pathogenic mechanisms, gradually forming a vicious cycle that further establishes a state of comorbidity []. SCI often leads to the occurrence of pain‒depression comorbidity (PDC) [, ]. Primary spinal cord injuries are typically attributed to localized trauma, which activates a series of biochemical cascades that result in secondary injury and delayed neuronal death [, ]. Our previous research demonstrated that neuroinflammation during acute SCI is a key component of the secondary response mechanism, leading to the recruitment and activation of microglia and astrocytes []. Microglia function like macrophages in early immune responses, particularly in the production of inflammatory mediators under pathological conditions within neural tissue []. Unlike other neurodegenerative diseases, SCI is characterized by the significant disruption of the blood‒brain‒spinal–cord barrier, which exacerbates peripheral macrophage infiltration and leads to the widespread production of inflammatory mediators [–]. This inflammatory response may persist throughout an individual’s lifetime [, ]. NP involves pathological changes in both the central and peripheral nervous systems, such as neuronal hyperexcitability, synaptic reshaping, and neuroinflammation. The extensive amplification of inflammation not only leads to the excitability of pain-related nerve fibres, such as those in the dorsal horn of the spinal cord (SDH), but also further contributes to pain hypersensitivity []. Prolonged neuroinflammation-mediated neuroimmune crosstalk may serve as the pathological basis for chronic pain and concurrent depressive symptoms []. Nicotinic acetylcholine receptors (nAChRs) play a significant role in the CNS, especially in the regulation of functions such as mood, learning, and memory [–]. Nicotine-related compounds have demonstrated antidepressant effects, with nAChRs involved in the modulation of depression [–]. Increasing evidence indicates that neuronal nAChRs expressed in the CNS serve as drug targets for the treatment of various neurodegenerative diseases, neurodevelopmental disorders, pain, and addiction [, ]. Furthermore, nAChR agonists constitute a class of candidate analgesics being evaluated for pain management [, , ]. Our previous research revealed that following SCI, β2*nAChR-mediated nicotinic cholinergic neurotransmission is significantly suppressed, accompanied by widespread neuroinflammation and promoting β2 nAChR expression enhances neurogenesis and improves motor function []. The most abundant nAChRs in the CNS are the heteromeric α4β2 and homomeric α7 nAChR subtypes []. Varenicline is a potent partial agonist of the α4β2*nAChR (Ki = 0.4 nM, efficacy = 45%) [] and is currently widely used for smoking cessation in individuals with nicotine addiction []. Varenicline has a good safety profile and favourable pharmacokinetic characteristics [, ].