Accepted

The development of restless legs syndrome (RLS) has been rarely reported during and following opioid withdrawal. We aimed to determine the presence and severity of RLS symptoms during and after supervised opioid tapering.

A major concern with cannabis-based medicines and medical cannabis (CbM) is the risk of abuse and dependence. The face validity of the International Classification of Diseases (ICD-10) criteria for cannabis dependence in patients prescribed CbM for chronic pain has not been assessed.

The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. : NCT01719055 (ClinicalTrials.gov).

The aim of this study was to analyze the effects of ten sessions of active transcranial direct current stimulation transcranial direct current stimulation (tDCS) (2 mA) with 13:20:13 stimulation at M1 in women with fibromyalgia (FM). To the best of our knowledge, this is the first article that uses this protocol in patients with FM. The main hypothesis is that the protocol would be effective in decreasing pain and that the results would last for up to 90 days.

Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.

Despite the available knowledge on underlying mechanisms and the development of several therapeutic strategies, optimal management of postoperative pain remains challenging. This pre-clinical study hypothesizes that, by promoting an anti-inflammatory scenario, pre-emptive administration of IMT504, a non-coding, non-CpG oligodeoxynucleotide with immune modulating properties, will reduce postincisional pain, also facilitating therapeutic opioid-sparing. Male adult Sprague-Dawley rats with unilateral hindpaw skin-muscle incision received pre-emptive (48 h and 24 h prior to surgery) or postoperative (6h after surgery) subcutaneous vehicle (saline) or IMT504. Various groups of rats were prepared for pain-like behaviour analyses, including subgroups receiving morphine or naloxone, as well as for flow-cytometry or quantitative RT-PCR analyses of the spleen and hindpaws (for analysis of inflammatory phenotype). Compared to vehicle-treated rats, pre-emptive IMT504 significantly reduced mechanical allodynia by 6 h after surgery, and accelerated recovery of basal responses from 72 h after surgery and onwards. Cold allodynia was also reduced by IMT504. Postoperative administration of IMT504 resulted in similar positive effects on pain-like behaviour. In IMT504-treated rats, 3 mg/kg morphine resulted in comparable blockade of mechanical allodynia as observed in vehicle-treated rats receiving 10 mg/kg morphine. IMT504 significantly increased hindpaw infiltration of mesenchymal stem cells, CD4+T and B cells, and caused upregulated or downregulated transcript expressions of interleukin-10 and interleukin-1β, respectively. Also, IMT504 treatment targeted the spleen, with upregulated or downregulated transcript expressions, 6 h after incision, of interleukin-10 and interleukin-1β, respectively. Altogether, pre-emptive or postoperative IMT504 provides protection against postincisional pain, through participation of significant immunomodulatory actions, and exhibiting opioid-sparing effects.

Previous literature has rarely examined the role of pain in the process of disablement. We investigate how pain associates with disability transitions among older adults, using educational attainment as a moderator. Data are from the National Health and Aging Trends Study, N=6,357; 33,201 one-year transitions between 2010-2020. We estimate multinomial logistic models predicting incidence or onset of and recovery from functional limitation and disability. Results show pain significantly predicts functional limitation and disability onset one year after a baseline observation, and decreases odds of recovery from functional limitation or disability. Contrary to expectations, higher education does not buffer the association of pain in onset of disability, but supporting expectations, it facilitates recovery from functional limitation or disability among those with pain. The analysis implicates pain as having a key role in the disablement process and suggests that education may moderate this with respect to coping with and subsequently recovering from disability.

It is currently unknown which pain-related factors contribute to long-term disability and poorer perceived health among older adults with chronic low back pain (LBP). This investigation sought to examine the unique influence of movement-evoked pain (MeP) and widespread pain (WP) on longitudinal health outcomes (i.e., gait speed, perceived disability, and self-efficacy) in 250 older adults with chronic LBP. MeP was elicited with three standardized functional tests, while presence of WP was derived from the McGill Pain Map. Robust regression with HC3 standard errors was used to examine associations between these baseline pain variables and health outcomes at 12-month follow-up. Covariates for these models included age, sex, body mass index, resting and recall LBP intensity, LBP duration, depression, pain catastrophizing, and baseline outcome (e.g., baseline gait speed). Greater MeP was independently associated with worse 12-month LBP-related disability (b=0.384, t=2.013, p=0.046) and poorer self-efficacy (b=-0.562, t=-2.074, p=0.039); but not gait speed (p>0.05). In contrast, WP and resting and recall LBP intensity were not associated with any prospective health outcome after adjustment (all p>0.05). Compared to WP and resting and recall LBP intensity, MeP is most strongly related to longitudinal health outcomes in older adults with chronic LBP. Perspective: This article establishes novel independent associations between MeP and worse perceived disability and self-efficacy at 12-months in older adults with chronic LBP. MeP likely has biopsychosocial underpinnings and consequences and may therefore be an important determinant of health outcomes in LBP and other geriatric chronic pain populations.

Central post-stroke pain (CPSP) is a type of central neuropathic pain, whose underlying mechanisms remain unknown. We previously reported that bilateral carotid artery occlusion (BCAO)-induced CPSP model mice showed mechanical hypersensitivity and decreased mRNA levels of preproorexin, an orexin precursor, in the hypothalamus. Recently, nicotine was shown to regulate the neuronal activity of orexin in the lateral hypothalamus (LH) and suppress inflammatory and neuropathic pain. In this study, we evaluated whether nicotine could suppress BCAO-induced mechanical allodynia through the activation of orexinergic neurons. Mice were subjected to BCAO for 30 min. Mechanical hypersensitivity was assessed by the von Frey test. BCAO mice showed hypersensitivity to mechanical stimuli three days after BCAO surgery. The intracerebroventricular injection of nicotine suppressed BCAO-induced mechanical hypersensitivity in a dose-dependent manner. These effects were inhibited by α7 or α4β2-nicotinic receptor antagonists. After nicotine injection, the level of c-fos, a neuronal activity marker, increased in the LH and locus coeruleus (LC) of Sham and BCAO mice. Increased number of c-Fos-positive cells partly colocalized with orexin A-positive cells in the LH, as well as tyrosine hydroxylase-positive cells in the LC. Orexinergic neurons project to the LC area. Nicotine-induced antinociception tended to cancel by the pretreatment of SB334867, an orexin receptor1 antagonist into the LC. Intra-LH microinjection of nicotine attenuated BCAO-induced mechanical hypersensitivity. Nicotine-induced antinociception was inhibited by intrathecal pre-treatment with yohimbine, an α2 adrenergic receptor antagonist. These results indicated that nicotine may suppress BCAO-induced mechanical hypersensitivity through the activation of the descending pain control system via orexin neurons.