Review Microglial Activation in Nociplastic Pain: From Preclinical Models to PET Neuroimaging and Implications…, 2025, Coluzzi+

[SNT Gatchaman]

Microglial Activation in Nociplastic Pain: From Preclinical Models to PET Neuroimaging and Implications for Targeted Therapeutic Strategies

Spoiler: Authors

Coluzzi, Flaminia; Zeboudj, Lynda; Scerpa, Maria Sole; Giorgio, Anna; De Blasi, Roberto Alberto; Malcangio, Marzia; Rocco, Monica

Nociplastic pain has recently been introduced as a third entity for identifying patients suffering from chronic pain that arises from altered nociception, without evidence of peripheral nociceptors activation or alterations of the somatosensory system. Currently, the main challenge of nociplastic pain is that it remains a diagnosis of exclusion, since no specific biomarkers are available.

Positron emission tomography (PET) neuroimaging studies, using selective translocator protein (TSPO) radiopharmaceuticals, specific for microglia activation, showed a strong correlation between neuroinflammation and nociplastic pain: in particular, in fibromyalgia (FM), which is the prototype disease. Neuroimaging studies identified key brain changes associated with pain processing and neuroinflammation in patients suffering from widespread pain, often associated with sleep, mood disorders, and cognitive impairment.

The present review will provide an overview on the role of neuroinflammation in nociplastic pain, focusing on preclinical evidence of microglia activation and advances in PET neuroimaging. Understanding the role of neuroinflammation could have relevant implications in selecting targeted therapeutic strategies and improving analgesic efficacy.

Web | DOI | PDF | International Journal of Molecular Sciences | Open Access

 

[Utsikt]

Understanding the exact mechanism underlying NcplP is a key factor for a targeted therapeutic strategy. Current pharmacological therapies are indeed burdened by several side effects, which may significantly affect the QoL of patients. Moreover, the minor perceived effects of pain relief led to low compliance and a high rate of discontinuation [30].

Different non-pharmacological therapies have been proposed as first line treatments in FM [147], some of which have been shown to have effects on neuroinflammation. Exercise showed promising results against neuroinflammatory processes, both in preclinical models [148,149] and in clinical studies [150]. Psychological interventions, including mindfulness [151] and cognitive behavioral treatment [152], may play an important role in FM management [153] through the modulation of neuroinflammation [154].

I do not understand the point of a review if you’re just going to parrot whatever is stated in abstracts. There is no uncertainty here, the trails are so seriously flawed that they might as well not have been done at all.

When such options are ineffective, pharmacological approaches should be considered [155]. Non-steroidal anti-inflammatory and steroids are not recommended, because they cannot suppress or mitigate neuroinflammatory process drugs [156]. Moreover, their long-term use should be avoided due to the risk of gastrointestinal, cardiovascular and renal side effects.

I thought it was only speculated that «neuroinflammation» was the cause of the pain?

Opioids are part of the pharmacological treatment of chronic pain; however, no efficacy has been demonstrated for NcplP [157].

There consensus statement from 2016 found no data on opioids for FM. So while «no efficacy has been demonstrated» might be technically correct, it would probably be more accurate to say that it hasn’t been tested in a trial setting.

Traditional strong opioids are discouraged because of warnings about their safety [158]. Nonetheless, dual and multi-mechanistic opioids, such as tramadol, tapentadol or buprenorphine, which also target pain modulatory pathways, could be clinically useful in a small proportion of patients [159,160], since serotonin and norepinephrine have pivotal roles in NcplP [161]. They should be used at the lowest possible dose, for the shortest period of time.

Again, they’ve just spent an entire paper explaining how all they have are hypotheses, and now things magically have pivotal roles.

Accordingly, antidepressants, such as tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors, in particular venlafaxine and duloxetine, are currently used as pharmacological options in FM [162]. Among anticonvulsants, PGB and gabapentin [163,164] are the most commonly used and investigated. Both classes of adjuvants counteract neuroinflammatory responses [165,166,167,168].

Recent preclinical and clinical investigations support targeting neuroinflammation, namely activated microglia, as a possible strategy to minimize drug-related adverse effects and to potentiate analgesic effectiveness. Um-PEA results a promising lipid mediator, which may be used as add-on therapy in NcplP, because of its extensively documented anti-inflammatory, analgesic, immunomodulatory, antimicrobial and neuroprotective effects [169].

Are you sure you got in all of the buzzwords?

 

[alktipping]

all those authors to publish a paper that any LLM can spit out in a minute. Makes you proud of our educations systems lack of standards .