scholarly journals Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain

Pain ◽  
2018 ◽  
Vol 159 (11) ◽  
pp. 2347-2362 ◽  
Author(s):  
Max A. Odem ◽  
Alexis G. Bavencoffe ◽  
Ryan M. Cassidy ◽  
Elia R. Lopez ◽  
Jinbin Tian ◽  
...  
2019 ◽  
Vol 374 (1785) ◽  
pp. 20190277 ◽  
Author(s):  
Edgar T. Walters

Chronic pain is considered maladaptive by clinicians because it provides no apparent protective or recuperative benefits. Similarly, evolutionary speculations have assumed that chronic pain represents maladaptive or evolutionarily neutral dysregulation of acute pain mechanisms. By contrast, the present hypothesis proposes that chronic pain can be driven by mechanisms that evolved to reduce increased vulnerability to attack from predators and aggressive conspecifics, which often target prey showing physical impairment after severe injury. Ongoing pain and anxiety persisting long after severe injury continue to enhance vigilance and behavioural caution, decreasing the heightened vulnerability to attack that results from motor impairment and disfigurement, thereby increasing survival and reproduction (fitness). This hypothesis is supported by evidence of animals surviving and reproducing after traumatic amputations, and by complex specializations that enable primary nociceptors to detect local and systemic signs of injury and inflammation, and to maintain low-frequency discharge that can promote ongoing pain indefinitely. Ongoing activity in nociceptors involves intricate electrophysiological and anatomical specializations, including inducible alterations in the expression of ion channels and receptors that produce persistent hyperexcitability and hypersensitivity to chemical signals of injury. Clinically maladaptive chronic pain may sometimes result from the recruitment of this powerful evolutionary adaptation to severe bodily injury. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1774.2-1774
Author(s):  
N. Jain ◽  
N. Reddy ◽  
A. Moorthy

Background:Cannabinoids has recently gained popularity for use in chronic pain. There is a lot of inquisitiveness among our patients wherein health care professionals are asked about its efficacy, side effects and sometimes even ask for a prescription! As there is paucity of data and research about its use in rheumatology, patient reported outcome(PROM) can guide ahead in expanding our knowledge and experience.Objectives:To study usage of cannabinoids by rheumatology patientsTo study awareness among primary physicians regarding Cannabinoid usage in rheumatology.Methods:Cross sectional survey with two arms. Arm 1 Information from patients attending tertiary rheumatology clinic,including perception regarding the use of Cannabinoids.Arm 2 consisted of collecting data via web-based survey with20-question from 100 GPs of Leicestershire. Questions on demographics, perspectives on and knowledge of cannabinoid use. Statistical analysis SPSS software.Results:Arm1 Total 102 rheumatology patients with 60%were females and 45% secondary education. 48% were unemployed. 75% Caucasians, 18% Asians. RA most common diagnosis followed by OA and FMS. 40 % depression and anxiety in addition to Rheumatic disease. 94% reported ongoing pain with 6-8 on a VAS scale. 79% were satisfied with their current therapy. 65% had heard about complementary medicine and 15% reported using cannabinoids.Most common form Cannabinoids oil 60% followed by smoking 20%. 56% reported using >3 months and majority 72% use daily. Median age 55 years. 88% users Caucasians. Mean disease duration 6.25 years among users indicates chronicity of disease has a direct proportion in usage. All users had ongoing pain of 7 on VAS. 87% believed it helps them managing pain effectively with a pain free state. On an average spends between 50-100 pounds per week. More than half believe cannabinoids should be available as a prescription drug in NHS and 30% interested to know more about it.In Arm 2 consisting of Primary care physicians, response rate 50%. Average clinical experience 5 years. Only 20% heard about usage of complementary medicine by rheumatology patient. Most replied that 10% of their patients use Cannabinoids for pain management. Most did not believe use of cannabinoids benefited the patients. Only 4% recommend its usage. 25% think it should be available as prescription. 40% experienced patients asking about cannabinoids during appointment. 88% of respondents did not know much about cannabinoid usage in rheumatology and have never prescribed it in their practice.Conclusion:Cannabinoids widely used by the rheumatology patients with PROM favouring its efficacy for control of chronic pain. Preclinical data suggest that cannabinoids might have a therapeutic potential RA1, OA, FMS2. Clinical data regarding cannabinoid treatment for rheumatic diseases are scarce, therefore, recommendations concerning cannabinoid treatment cannot be made. All patients who reported using it suffered from moderate to severe chronic pain. Thus main indication of usage was pain rather than recreational purpose. Although a small survey it clearly highlights lack of knowledge among primary physicians. These results emphasise the need for further research regarding the benefits and risks of cannabinoids in rheumatology.References:[1]RichardsonD. etal Characterisation ofthe cannabinoid receptor system in synovial tissue andfluid in patients with OA and RA Arthritis Res.Ther. 10, R43 (2008).[2]Walitt, B etal Cannabinoids for fibromyalgia. Cochrane DatabaseSyst. Rev. 7, CD011694 (2016).Disclosure of Interests:Nibha Jain: None declared, Neelima Reddy: None declared, Arumugam Moorthy Speakers bureau: Abbvie, Novartis,UCB,MSD


2019 ◽  
Vol 26 (1) ◽  
pp. 19-26
Author(s):  
Esther Jun ◽  
Samina Ali ◽  
Maryna Yaskina ◽  
Kathryn Dong ◽  
Manasi Rajagopal ◽  
...  

Abstract Background Given the current opioid crisis, caregivers have mounting fears regarding the use of opioid medication in their children. We aimed to determine caregivers’ a) willingness to accept, b) reasons for refusing, and c) past experiences with opioids. Methods A novel electronic survey of caregivers of children aged 4 to 16 years who had an acute musculoskeletal injury and presented to two Canadian paediatric emergency departments (ED) (March to November 2017). Primary outcome was caregiver willingness to accept opioids for moderate pain for their children. Results Five hundred and seventeen caregivers participated; mean age was 40.9 (SD 7.1) years with 70.0% (362/517) mothers. Children included 62.2% (321/516) males with a mean age of 10.0 (SD 3.6) years. 49.6% of caregivers (254/512) reported willingness to accept opioids for ongoing moderate pain in the ED, while 37.1% (190/512) were ‘unsure’; 33.2% (170/512) of caregivers would accept opioids for at-home use, but 45.5% (233/512) were ‘unsure’. Caregivers’ primary concerns were side effects, overdose, addiction, and masking of diagnosis. Caregiver fear of addiction (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.25) and side effects (OR 1.25, 95% CI 1.11 to 1.42) affected willingness to accept opioids in the emergency department; fears of addiction (OR 1.19, 95% CI 1.07 to 1.32), and overdose (OR 1.15, 95% CI 1.04 to 1.27) affected willingness to accept opioids for at-home use. Conclusions Only half of the caregivers would accept opioids for moderate pain, despite ongoing pain following nonopioid analgesics. Caregivers’ fears of addiction, side effects, overdose, and masking diagnosis may have influenced their responses. These findings are a first step in understanding caregiver analgesic decision making.


1995 ◽  
Vol 74 (5) ◽  
pp. 2100-2125 ◽  
Author(s):  
D. M. Snodderly ◽  
M. Gur

1. In alert macaque monkeys, multiunit activity is encountered in an alternating sequence of silent and spontaneously active zones as an electrode is lowered through the striate cortex (V1). 2. Individual neurons that are spontaneously active in the dark usually have a maintained discharge in the light. Because both types of discharge occur in the absence of deliberate stimulation, we call them the "ongoing" activity. The zones with ongoing activity correspond to the cytochrome oxidase (CytOx)-rich geniculorecipient layers 4A, 4C, and 6, whereas the adjacent layers 2/3, 4B, and 5 have little ongoing activity. 3. The widths of receptive field activating regions (ARs) are positively correlated with the cells' ongoing activity. Cells with larger ARs are preferentially located in the CytOx-rich (input) layers, and many are unselective for stimulus orientation. However, approximately 90% of the cells in the silent layers are orientation selective, and they often have small ARs. 4. The laminar distribution of selectivity for orientation and direction of movement in alert animals is consistent with earlier results from anesthetized animals, but the laminar distribution of AR widths differs. In alert macaques, the ARs of direction-selective cells in layer 4B and of orientation-selective cells in layer 5 are among the smallest in V1. 5. Our findings indicate that the input layers of V1 (4A, 4C, and 6) have a diversity of AR widths, including large ones. Cortical processing produces receptive fields in some of the output layers (4B and 5) that are restricted to small ARs with high resolution of spatial position. These results imply potent lateral and/or interlaminar interactions in alert animals in early cortical processing. The diversity of AR widths generated in V1 may contribute to detection of fine detail in the presence of contrasting backgrounds--the early stages of figure-ground discrimination.


2017 ◽  
Vol 3 ◽  
Author(s):  
Albert Albers ◽  
Matthias Behrendt ◽  
Simon Klingler ◽  
Nicolas Reiß ◽  
Nikola Bursac

Most products are developed in generations. This needs to be considered with regard to development methods and processes to make existing knowledge available to achieve increased efficiency. To realize this, the approach of PGE – product generation engineering – is formulated. Product generation engineering is understood as the development of products based on reference products (precursor or competitor products). The subsystems are either adapted to the new product generation by means of carryover or they are newly developed based on shape variation or principle variation. Validation is considered as the central activity in the product engineering process and is a major challenge, especially for complex mechatronic systems. Therefore, it is important to understand validation as an ongoing activity during product development. The pull principle of validation describes the definition and development of validation activities, including models and validation environments based on specific validation objectives. In order to have effectiveness within validation of subsystems, it is necessary to map the interactions with the overall system, namely the super-system. The relevant subsystems can be connected under consideration of functional and energetic aspects by means of virtual, physical or mixed virtual–physical modeling applied by the holistic IPEK-X-in-the-Loop approach within the integrated Product engineering Model (iPeM).


2016 ◽  
Vol 17 (3) ◽  
pp. 374-382 ◽  
Author(s):  
Joshua Havelin ◽  
Ian Imbert ◽  
Jennifer Cormier ◽  
Joshua Allen ◽  
Frank Porreca ◽  
...  

2021 ◽  
Author(s):  
Anton Filipchuk ◽  
Alain Destexhe ◽  
Brice Bathellier

AbstractNeural activity in sensory cortex combines stimulus responses and ongoing activity, but it remains unclear whether they reflect the same underlying dynamics or separate processes. Here we show that during wakefulness, the neuronal assemblies evoked by sounds in the auditory cortex and thalamus are specific to the stimulus and distinct from the assemblies observed in ongoing activity. In contrast, during anesthesia, evoked assemblies are indistinguishable from ongoing assemblies in cortex, while they remain distinct in the thalamus. A strong remapping of sensory responses accompanies this dynamical state change produced by anesthesia. Together, these results show that the awake cortex engages dedicated neuronal assemblies in response to sensory inputs, which we suggest is a network correlate of sensory perception.One-Sentence SummarySensory responses in the awake cortex engage specific neuronal assemblies that disappear under anesthesia.


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