pain (,:ALL YOU OUGHT TO KNOW .BY MOHAMED RIFKY

ALL THAT YOU OUGHT TO KNOW ABOUT PAIN BY MOHAMED ANWER RIFKY

1. PAIN 1-HISTORY 2-DEFINITION 3-PAIN PASS WAYS 4-TYPES OF PAIN 5-MANIFESTATIONS OF UNTREATED PAIN 6-MANEGEMENT OF PAIN,INCLUDING OTHER MODALITIES 7-CLASSIFICATION OF PAIN 8-PAIN SCALES MOHAMED ANWER RIFKY ALL WHAT YOU OUGHT TO KNOW ABOUT

2.   Ancient Civilizations : Ancient Egyptians, Greeks, and Romans used various herbal **r emedies, including opium, to manage pain. Traditional Chinese medicine also incorporated techniques like acupuncture and herbal therapies to alleviate pain. Middle Ages and Renaissance: The use of opioids , such as opium and its derivatives, continued in the Middle Ages and Renaissance periods. Advances in anatomy and physiology led to a better understanding of the nature of pain. PAIN HISTORY ** medicine or therapy that cures disease or relieve pain 19th Century: The discovery of anesthesia , including the use of ether and chloroform, revolutionized surgical procedures and pain management. The development of morphine and other opioid analgesics further expanded pain management options. 20th Century: The gate control theory of pain, proposed by Ronald Melzack and Patrick Wall in 1965, provided a new understanding of pain perception and paved the way for the development of novel pain management strategies. The World Health Organization (WHO) introduced the pain relief ladder in the 1980s, which became a widely adopted approach for the management of cancer pain . The concept of " pain as the fifth vital sign " gained prominence in the 1990s, leading to increased emphasis on pain assessment and management in healthcare. The use of non-opioid analgesics , such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), as well as adjuvant therapies like antidepressants and anticonvulsants, expanded the pain management arsenal. Interventional pain management techniques , including nerve blocks, spinal cord stimulation, and intrathecal drug delivery, emerged as important tools for managing chronic and intractable pain. Here are some links that provide more detailed information on the history of pain management “The History of Pain Management" by Bengt Winblad : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172100/ "The History of Pain Management" by the American Chronic Pain by the American Society of Anesthesiologists : https://www.asahq The   Code of Hammurabi , a collection of 282 rules from ancient ** Mesopotamia, included provisions for the management of pain. The  Edwin Smith Papyrus , a medical manuscript from 1500 BC , contains descriptions of surgical techniques for the treatment of pain, demonstrating the Egyptians ’ advanced understanding of pain control. ** land between the Tigris and Euphrates;

3. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage ” ( Raja et al., 2020 ). PAIN DEFINITION On individuality – pain is a uniquely personal experience that is impacted by a wide host of not only biological but also psychological and social factors, which is often subjective and can vary widely from person to person ( Fillingim , 2017 ). Despite no clear threshold on when persistent pain is classified as “chronic,” the IASP has generally accepted that pain persisting beyond an anticipated three-month healing period is pathological ( Treede et al., 2019 ). Peripheral somatosensory fibers that are involved in pain sensation include A- δ and C fibers ( Dinakar and Stillman, 2016 ). A- δ fibers are implicated in sharp or prickling pain sensations and may respond to intense mechanical stimulation, noxious mechanical stimulation, and heat at both innocuous and noxious temperatures ( Watson, 1981 ). Conversely, C fibers are often thought to be involved in more intense burning pain sensations and are polymodal , responding to noxious mechanical, thermal, and chemical irritant stimuli ( Watson, 1981 ). Congenital insensitivity to pain The most striking demonstration of a genetic influence on the pain experience is in patients suffering from congenital insensitivity to pain (CIP). An extremely rare condition, CIP is characterized by the inability to feel pain from noxious stimuli, including inflammation and heat, from birth ( Schon et al., 2020 ). This often manifests in young children as cuts, bruises, and burns from impaired temperature sensation as well as self-mutilating injuries , commonly to the fingertips, tongue, or teeth ( Cox et al., 2006 ). In older individuals , CIP may present as recurrent fractures , joint damage, or bony deformities due to past trauma ( Schon et al., 2020; Staudt et al., 2018 ). A simplified schema of a spinal nerve and the different types of fibers contained there in (DC, dorsal columns; STT, spinothalamic tract) (adapted from Byers MR, Bonica JJ. Peripheral pain mechanisms and nociceptor plasticity. In: Loeser JD, Butler SH, Chapman CR, Turk DC, editors. Bonica’s management of pain. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2001. Complex Chronic Pain (CCP) is a term used to describe a type of chronic pain that is characterized by a combination of physical, psychological, and social factors that contribute to the development and maintenance of the pain experience . pain is out of proportion to the severity of the initial injury.

4.   PAIN PASS WAY Peripheral Receptors: Pain receptors, also called nociceptors, are specialized nerve endings located in the skin, muscles, joints, and internal organs. These receptors detect various types of painful stimuli, such as mechanical, thermal, or chemical. Primary Afferent Neurons: The pain signals from the peripheral receptors are transmitted through the primary afferent neurons. These neurons have their cell bodies in the dorsal root ganglia (DRG) or the trigeminal ganglia (for the face and head). Spinal Cord and Brainstem: The primary afferent neurons enter the spinal cord through the dorsal root and synapse with secondary neurons in the dorsal horn of the spinal cord. From the spinal cord, the pain signals are transmitted to the brainstem, specifically the midbrain, pons, and medulla oblongata. Thalamus: The pain signals from the brainstem are then relayed to the thalamus, which acts as a relay station for various sensory information, including pain. Cerebral Cortex: The thalamus projects the pain signals to the primary somatosensory cortex , where the perception of pain is localized and ** perceived. The pain signals may also be further processed in other cortical and subcortical regions , such as the prefrontal cortex, limbic system, and insular cortex, which are involved in the emotional and cognitive aspects of pain experience . ** The diencephalon encloses a cavity called the third ventricle ** Detected by means of the senses   The nociceptive system, which consists of peripheral, small myelinated, and unmyelinated nociceptive afferent neurons that project to the spinal cord dorsal horn where second-order neurons process the incoming nociceptive information. Axons from spinal projection neurons travel through the anterolateral tract of the spinal cord and project to supraspinal sites in the brainstem, midbrain , and **diencephalon, where they terminate in the h ypothalamus and different regions of the thalamus . Third-order neurons send axons to cortical areas, including the cingulate and the insula , and subcortical structures, such as the limbic system . Nociceptive signaling includes transduction of noxious stimuli to action potentials in the periphery , transmission of these nerve signals to the central nervous system, mo dulation of the sensory information at multiple sites along the nociceptive pathway, and finally the perception at the level of the brain. Signals originating in the cerebral cortex as well as the spinothalamic tract pass through the periaqueductal gray matter in the midbrain. A signal as an action potential is generated there which then travels to the pons ( locus coeruleus) and medulla (locus raphe magnus ) . From there, another action potential is generated that travels down the spinal cord through the dorsolateral tract, terminating upon an interneuron near the synapse between the primary and secondary afferent neurons. At that level, inhibitory signals are sent by the interneuron, which alters or inhibits ( modulates) the pain signals traveling to the brain by decreasing the release of glutamate and substance P from the presynaptic terminals of the primary afferent axons and reducing the postsynaptic excitatory signals originating in the postsynaptic terminal of the secondary afferent axons. Many neurotransmitters are involved here as well, including norepinephrine, serotonin, and primarily endogenous opioids (enkephalins). This is part of the gate theory, proposed by Melzack and Wall in 1965.

5. 1- Another prominent pathway is the spino­reticular tract , which is involved in noci­ceptive processing. The spino ­-reticular tract is similar to the spino­thalamic tract in that it is excited by similar sensory fibers. Rather than ascending to the thalamus however, spino­reticular neurons terminate within the brainstem. The trigeminal nerve (which carries nociception from face and head) whose cell bodies are located outside of the spinal cord, in the trigeminal ganglion, and which synapses with the central nervous system at the nucleus caudalis in the medulla. 2- The development of computed tomography (CT) and, soon thereafter, magnetic resonance imaging (MRI), allowed researchers to look into the living brain and gain some understanding of the parts of the brain affected by certain types of pain. The development of positron emission tomography (PET) has allowed researchers, for the first time, to investigate neuronal activity throughout the entire brain (Casey, 2015). Other imaging studies have reported structural changes in the brains of patients with chronic low back pain . One study found that these patients showed 5% to 11% less neocortical gray matter volume than control subjects and that the decreased volume was related to pain duration . These studies indicate that chronic low back pain is also associated with structural pathologic changes in the brain (Kong et al., 2013). 3- We can become sensitized to pain. Sensitization is a neurophysiologic term that describes the increased responsiveness of nociceptive neurons (the pain pathways become more sensitive ). Hyperalgesia (exaggerated responses to stimuli) and allodynia (see above) are clinical markers used to detect the presence of sensitization ( Zouikr et al., 2016). There are two types of sensitization: peripheral and central. Peripheral sensitization occurs in response to the release of inflammatory molecules such as histamine, prostaglandins, and pro-inflammatory cytokines . In central sensitization , nociceptive-specific neurons may progressively increase their response to repeated non-painful stimuli, develop spontaneous activity, and increase the area of the body that is involved with the pain. Exaggerated response to a given noxious stimulus ( hyperalgesi a) develops and spreads to uninjured tissue (secondary hyperalgesia). The cerebral signature of pain

6. Physiologic Effects of Unrelieved Pain Unrelieved pain is a stressor that can lead to physiologic changes and negative effects on the endocrine, cardiovascular, gastrointestinal, and immune systems . The endocrine system reacts to unrelieved pain by releasing an excessive amount of hormones, ultimately resulting in carbohydrate, protein, and fat catabolism , poor glucose utilization, and other harmful effects. This reaction combined with inflammatory processes can produce weight loss, tachycardia, increased respiratory rate, fever, shock, and death. The cardiovascular system responds to the stress of unrelieved pain by activating the sympathetic nervous system . Following a surgical procedure, for example, this can include hypercoagulation and increased heart rate , blood pressure, cardiac workload, and oxygen demand. Since the stress response causes an increase in sympathetic nervous system activity, intestinal secretions and smooth muscle sphincter tone increase , and gastric emptying and intestinal motility decrease. This response can cause temporary impairment of gastrointestinal function and increase the risk of ileus (intestinal obstruction). Aggressive pain control may be needed to reduce these effects and prevent thromboembolic complications . Unrelieved pain may be especially harmful for patients with metastatic cancers . Stress and pain can suppress immune function, including the natural killer cells that play a role in preventing tumor growth and controlling metastasis. Preemptive analgesia refers to the administration of an analgesic (pain medication) before a painful stimulus, with the goal of preventing or reducing the development of central sensitization and hyperalgesia (increased pain sensitivity) that can occur after tissue injury or surgical procedures. Neuropathic Pain resulting from injury to, inflammation of, or dysfunction of the peripheral or central nervous system ,as complex regional pain syndrome (CRPS), phantom limb pain, Guillain-Barré syndrome, sciatica shown as,spontaneous ; burning; lancinating or shooting; dysesthesias (pins and needles, electrical sensations); hyperalgesia (amplification of noxious stimuli); hyperpathia (widespread pain in response to a discrete noxious stimulus); allodynia (pain in response to nonpainful stimulation); pain may be perceived distal or proximal to site of injury, often corresponding to innervation pathways (e.g., sciatica)

7. Classification of pain There are many ways of classifying pain. Examples include by duration , aetiology or anatomical location. Duration: Pain is commonly described as acute or chronic pain. Aetiology : Pain may also be classified as physiological or pathological . Physiological pain occurs in the absence of actual tissue or nerve damage, serving as a warning sign for impending injury. Examples include muscle cramp and abdominal colic. In pathological pain, tissue or nerve damage occurs. The activation of the pain system is commonly accompanied by its sensitisation Location: Pain may also be classified as either somatic or visceral (or a combination of both) depending on the anatomical nature of the tissue involved. Somatic pain from joints, muscle or skin is usually well localised . Visceral pain from internal organs is often poorly localised and diffuse due to inputs from multiple spinal segments and the convergence of afferents from neighbouring organs ( viscerovisceral convergence). Fibre type Aδ (finely myelinated) C (unmyelinated) Fibre diameter 2–5 μm <2 μm Conduction velocity 5–15 m/second 0.5–2 m/second Distribution Body surface, muscles, joints Most tissues Pain sensation Rapid, pricking, well localized Slow, diffuse, dull, aching Position of synapse within dorsal horn of spinal cord Laminae I and V Lamina II (substantia gelatinosa ) Referred Pain: This type of pain is felt in a different location from the source of the pain, often due to the overlap of nerve pathways. Examples include referred shoulder pain from a heart attack or referred abdominal pain from a gallbladder problem. Conscious perception of visceral sensations map to specific regions of the body, as shown in this chart. Some sensations are felt locally, whereas others are perceived as affecting areas that are quite distant from the involved organ. Dermatomal distribution in the adult. Overlapping distribution of segments is indicated for the trunk (adapted from Lockhart RD, Hamilton GF, Fyfe FW. Anatomy of the human body. Philadelphia: J.B. Lippincott Company; 1972)

8. The grey matter of the spinal cord was divided into ten separate laminae by Rexed in 1952. Laminae I to VI are located within the dorsal horn and the majority of nociceptors synapse in laminae I, II and V where they form primary synapses with either interneurons or dorsal horn neurons. The majority of C fibres terminate in lamina II which is also known as substantia gelatinosa (SG). Dorsal horn neurons, so-termed because their nuclei are located in the dorsal horn of the spinal cord, are second-order sensory neurons that transmit nociception from the spinal cord to higher centres in brain. Nociceptor afferents may also synapse with interneurons , which in turn synapse with dorsal horn neurons. Interneurons are present exclusively in the central nervous system and can be either excitatory or inhibitory . A dorsal horn neuron may be excited or inhibited depending on the type of interneuron that it configures with. This primary synapse with interneuron is central to the mechanism for modulating the sensitivity of the pain system. Excitatory interneurons release glutamate , the chief excitatory neurotransmitter , which binds with a variety of receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA ), N-methyl-D-aspartate (NMDA) and G-protein-coupled **metabotropic receptors . Inhibitory interneurons release γ-aminobutyric acid (GABA) and glycine as neurotransmitters. GABA binds to inotropic GABA A receptor (ligand-gated receptor) or G-protein-coupled metabotropic GABA B receptors (receptor). Glycine binds to inotropic glycine receptors. The glycine receptors are closely related to GABA A receptors, as they both open ion channels selectively permeable to the anion chloride which hyperpolarise the neuronal cell membranes. Inhibitory interneurons can be stimulated by primary afferents, the descending modulation system or Aβ fibres . With repeated or prolonged nociceptive stimulation , central sensitisation occurs at the spinal cord. This is an important process in the development and maintenance of chronic pain with the nervous system going through a process called ‘ ** wind-up ’ resulting in a persistent state of pain hypersensitivity . **provoking someone with persistent annoyances ** A metabotropic receptors are indirectly linked with ion channels through signal transduction mechanisms, such as  G proteins .

9. A numerical rating scale usually includes a horizontal line marked with the numbers 0–10. People point to or say the number that best represents the level of pain they are feeling. A  2018 review Trusted Source  suggests that adults with no cognitive impairments find the numerical rating scale easy to use. It also lets people be more specific than scales with fewer than 10 pain levels. Researchers often use numerical pain scales to gather data, as it is easy to interpret. A simple lines with “no pain” at one end and “severe pain” at the other. People mark a point between those extremes to demonstrate how much pain they are experiencing. One of the benefits of visual analog scales is that people can express their precise pain level. This can be useful for people who have long-term conditions with pain levels that vary over time. Visual analog scales are more sensitive tools for researchers, and less prone to bias. With verbal rating scales , people describe their pain verbally on a scale from “ mild” to “severe .”  Numerous studies Trusted Source  show that people find these scales easy to understand and use, while they provide reliable information. However, verbal rating scales are less sensitive compared to visual analog scales. They can also lead to miscommunication and may present a language barrier for people who do not speak their doctor’s language. In these cases, some may find numerical scales easier to use and interpret. 1-Unidimensional Scales OF PAIN 2-Multidimensional scales The  brief pain inventory (BPI) scale   is a short questionnaire that people fill out so healthcare professionals can assess a person’s pain, and how it impacts them. The BPI scale measures pain intensity, pain location , how much the pain interferes with daily life, and how much pain a person experiences within a certain time frame. It is available in many languages and contains pictures to help someone describe where their pain is. The BPI scale also looks at how long pain lasts, as well as pain medication. However, it does take more time to complete than a simpler pain scale. McGill pain questionnaire The McGill pain questionnaire (MPQ) is another questionnaire that people fill out by themselves to measure their pain. This pain scale is available in  17 different languages . In addition to pain severity, the MPQ measures how pain feels physically, allowing people to describe sensations such as burning or throbbing. It also looks at how this affects someone emotionally. This can be useful for assessing pain from long-lasting conditions. However, the variety of ways of describing pain with an MPQ can be a drawback, as it requires an understanding of its vocabulary . It is not suitable for children or adults who do not understand language such as “smarting.” Additionally, the MPQ takes longer to complete than other measuring pain techniques, making it less convenient. Faces Scales (e.g., FACES-R, Wong-Baker, Oucher , Bieri , McGrath scales) ** FLACC (Face, Legs, Activity, Cry, ** Consolability ) Scale: Used for infants and young children. CRIES (Crying, Requires oxygen, Increased vital signs, Expression, Sleepless) Scale: Used for newborns . ** Difficult to console or comfort (pushing away caregiver) .

10. Multimodal Analgesia TREATMENT OF PAIN Multimodal analgesia combines different classes of medications that have different ( multimodal ) pharmacological mechanisms of action, resulting in additive or synergistic effects to reduce postoperative pain and its sequelae. Such an approach may achieve desired analgesic effects while reducing analgesic dosage and associated side effects. Multimodal pain management often includes utilization of regional analgesic techniques , including local anesthetic wound infusion, epidural/intrathecal analgesia, or single shot/continuous peripheral nerve blockade. Multimodal analgesia is routinely utilized to improve postoperative outcomes. 1. NSAIDs — The addition of nonsteroidal anti-inflammatory drugs (NSAIDs) to systemic opioid analgesia diminishes postoperative pain intensity, reduces opioid requirements, and decreases opioid-related side effects such as PONV, sedation, and urinary retention. However, NSAIDs may increase the risk of gastrointestinal and wound bleeding , decrease kidney function , and impair wound healing . There is also a concern that NSAIDs may have a detrimental effect on anastomotic healing of the gastrointestinal tract and increase the risk of anastomotic leak, although this is controversial and further research is needed. Perioperative administration of selective cyclooxygenase-2 ( COX-2) inhibitor NSAIDs likewise reduces postoperative pain and decreases both opioid consumption and opioid-related side effects, and although their use reduces the incidence of NSAID-related platelet dysfunction and gastrointestinal bleeding, the potential adverse effects of COX-2 inhibitors on kidney function remain controversial. Concerns have also been raised, primarily with rofecoxib and valdecoxib, regarding COX-2 safety for patients undergoing cardiovascular surgery. Increased cardiovascular risk associated with the perioperative use of celecoxib or valdecoxib in patients with minimal cardiovascular risk factors and undergoing nonvascular surgery is unproven. Further studies are needed to establish the analgesic efficacy and safety of COX-2 inhibitors, their clinical impact on postoperative outcomes, and their precise role in ERPs. 2-Acetaminophen (paracetamol) — Oral, rectal, and parenteral acetaminophen is a common component of multimodal analgesia. Acetaminophen’s analgesic effect is 20% to 30% less than that of NSAIDs , but its pharmacological profile is safer. Analgesic efficacy improves when the drug is administered together with NSAIDs, and it significantly reduces pain intensity and spares opioid consumption after orthopedic and abdominal surgery. However, acetaminophen may not reduce opioid-related side effects . Routine administration of acetaminophen in combination with regional anesthesia and analgesia techniques may allow NSAIDs to be reserved for control of breakthrough pain, thus limiting the incidence of NSAID-related side effects. 3. Gabapentinoids — Oral gabapentin and pregabalin given as a single dose preoperatively have been shown to decrease postoperative pain and opioid consumption in the first 24 h following surgery. There is debate about the dose and duration of perioperative use of these drugs , and whether they may potentially alter the incidence of chronic pain after surgery. Common side effects include sedation and dizziness, especially in elderly patients . 4. N -methyl-D-aspartate (NMDA) receptor antagonists — Ketamine : Perioperative low-dose ketamine (bolus, infusion) has been associated with significant reduction in pain, opioid consumption, and PONV. Ketamine has also been shown to be of particular benefit in patients on chronic opioids. Magnesium: Magnesium may also reduce postoperative pain and opioid consumption, although the optimal dosing is uncertain. Side effects include hypotension and potentiation of neuromuscular blockade. 5. Intravenous lidocaine — Intravenous lidocaine infusion analgesia has recently increased in popularity because there is good evidence to support its use as a component of multimodal analgesia. In major abdominal surgery, it is associated with faster return of bowel function and decreased hospital length of stay. Continuous cardiovascular monitoring is frequently advocated for patients receiving intravenous lidocaine, and therefore its use is currently limited to settings such as the PACU, ICU , or a monitored hospital ward. However, several centers have developed and implemented perioperative protocols to safely use intravenous lidocaine on surgical wards without continuous cardiovascular monitoring. ** fairly new technique , Mesenchymal stem cells s cavenging nanomaterials facilitates the elimination of pro-inflammatory cytokines and ROS in microglia and ameliorates allodynia . Which are a cause of development of neuropathic pain . MSCs are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in the bone marrow, lungs, adipose tissue, and other body tissues. MSCs have the ability to differentiate into osteogenic,

11. 6. Opioids — Despite the increasing use of new, nonopioid analgesic medications and adjuvants and of regional anesthesia and analgesia techniques intended to minimize opioid requirements and opioid-related side effects, the use of systemic opioids remains a cornerstone in the management of surgical pain. Parenteral opioids are frequently prescribed in the postoperative period during the transitional phase to oral analgesia. Opioid administration by patient controlled analgesia (PCA) provides better pain control, greater patient satisfaction, and fewer opioid side effects when compared to nurse-administered, on-request (PRN) parenteral opioid administration. Oral administration of opioids, such as oxycodone or hydrocodone, in combination with NSAIDs or acetaminophen, or both, is common in the perioperative period . 7. Epidural analgesia — In addition to providing excellent analgesia, epidural blockade blunts the stress response associated with surgery, decreases postoperative morbidity, attenuates catabolism , and accelerates post operative functional recovery . Compared with systemic opioid analgesia, thoracic epidural analgesia provides better static and dynamic pain relief. However, these benefits have mainly been observed in patients undergoing open abdominal and thoracic surgery; its usefulness in patients undergoing minimally invasive abdominal and thoracic surgery is questionable, as recent trials have suggested it may actually prolong in-hospital recovery in such cases. Long-acting local anesthetics such as ropivacaine (0.2%), bupivacaine (0.0625–0.125%), and levobupivacaine (0.1–0.125%) are commonly administered together with lipophilic opioids by continuous epidural infusion or by patient-controlled epidural analgesia (PCEA) . As previously noted, administering low doses of local anesthetic via thoracic epidural infusion instead of lumbar levels avoids lower extremity motor blockade that may delay postoperative mobilization and recovery and will increase the risk of patient falls. Adding opioids to epidural local anesthetics improves the quality of postoperative analgesia without delaying recovery of bowel function without delaying recovery of bowel function. 7-Paravertebral nerve blocks — Paravertebral nerve blocks provide similar parietal analgesia to epidural blockade but without the risk of epidural-related side effects. However, they have been poorly studied in the context of ERPs. 9. Peripheral nerve blockade — Single-shot and continuous peripheral nerve blockade is frequently utilized for fast-track ambulatory and inpatient orthopedic surgery, and can accelerate recovery from surgery and improve both analgesia and patient satisfaction. For some procedures, blocking multiple nerves can provide analgesic benefits superior to blockade of a single nerve. The opioid-sparing effect of nerve blocks minimizes the risk of systemic opioid-related side effects. Appropriate patient selection and strict adherence to institutional clinical pathways helps ensure the success of peripheral nerve blockade as a fast-track orthopedic analgesia technique and also helps minimize its risks. Advances in ultrasound imaging technology and techniques have accelerated interest in abdominal wall blockade, facilitating the selective localization of specific nerves and the direct deposition of local anesthetic solutions in proximity to the compartments where specific nerves are located Single-shot perineural administration of liposomal bupivacaine has been used recently to extend the analgesic duration of peripheral nerve blocks to up to 72 h after surgery . However, preliminary studies have not consistently shown expected benefits, and the role of liposomal local anesthetic preparations in postoperative analgesia and ERPs has, therefore, yet to be precisely defined.   ** Enhanced recovery programme  (ERP )  10. High-volume local anesthetic infiltration analgesia and wound infusion — High-volume local anesthetic infiltration analgesia with a mixture of local anesthetic and epinephrine, with or without systemic NSAIDs , has recently gained popularity in patients undergoing total hip and knee replacements , and is currently replacing peripheral nerve blocks in many institutions, especially in the context of an **ERP .However, supporting evidence demonstrating that this technique is superior to peripheral nerve blockade is currently lacking. Moreover, its impact on metabolic and inflammatory responses and on non–analgesic-related outcomes remains unknown. The impact of peripheral nerve blocks and rehabilitation therapy on functional outcomes also remains incompletely studied. Local anesthetic wound infusions can be used to improve postoperative pain control and reduce the necessity for opioids, especially in patients undergoing open abdominal surgery and in whom epidural analgesia is contraindicated. The analgesic efficacy of local anesthetic wound infusion has been also established for multiple other surgical procedures. Inconsistent results from wound infusion may be secondary to type, concentration, and dose of local anesthetic employed; catheter placement; and mode of local anesthetic delivery. . 8 Composition: Liposomal bupivacaine is a formulation that encapsulates the local anesthetic bupivacaine within lipid-based vesicles called liposomes. This allows for a slower and more sustained release . Generalized diagram of G protein-gated ion channel: (A) Typically, the activated effector protein begins a signaling cascade which leads to the eventual opening of the ion channel. (B) The GTP-bound α-subunit in some cases can directly activate the ion channel. (C) In other cases, the activated βγ-complex of the G protein may interact with the ion channel.

12. 11. Intraperitoneal instillation and nebulization of local anesthetic — Instillation and nebulization of intraperitoneal local anesthetic decreases pain intensity and decreases opioid consumption following open abdominal and laparoscopic surgery . However, the precise roles of these techniques in multimodal management remain to be determined. ** Morphine 3-glucuronide and morphine 6-glucuronide , in patients with kidney failure has been associated with narcosis and ventilatory depression. ** Rapid administration of larger doses of opioids (particularly fentanyl, sufentanil , remifentanil, and alfentanil) can induce chest wall rigidity severe enough to make ventilation with bag and mask nearly impossible. ** Prolonged dosing of opioids can produce “opioid-induced hyperalgesia ,” in which patients become more sensitive to painful stimuli. ** I nfusion of large doses of (in particular) remifentanil during general anesthesia can produce acute tolerance, in which much larger than usual doses of opioids are required for postoperative analgesia. The neuroendocrine ** stress response to surgery is measured in terms of the secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol. Large doses of opioids inhibit the release of these hormones in response to surgery more completely than volatile anesthetics. ** Aspirin is unique in that it irreversibly inhibits COX-1 by acetylating a serine residue in the enzyme. The irreversible nature of its inhibition underlies the nearly 1-week persistence of its clinical effects ( e.g , inhibition of platelet aggregation to normal) after drug discontinuation. Surgical treatment of pain is often considered when other conservative or non-invasive treatments have failed to provide adequate relief. There are several surgical techniques that can be used to manage various types of pain, including: Neuromodulation Techniques: Spinal Cord Stimulation (SCS): This involves implanting a device that delivers electrical impulses to the spinal cord, which can help reduce certain types of chronic pain. Dorsal Root Ganglion (DRG) Stimulatio n: This technique targets the dorsal root ganglion, which is a collection of nerve cells, to provide pain relief. Peripheral Nerve Stimulation (PNS): This involves placing electrodes near a specific nerve to provide targeted electrical stimulation and pain relief. Surgical Lesioning Techniques: Radiofrequency Ablation (RFA): This procedure uses heat energy to selectively destroy specific nerve fibers , reducing pain signals. Cryoablation: This technique uses extreme cold to selectively destroy nerve fibers, providing pain relief. Cordotomy: This surgical procedure involves ** severing specific nerve pathways in the spinal cord to reduce pain signals. ** Cut off from a whole Intrathecal Drug Delivery Systems: Implantable Drug Pumps : These devices are surgically placed under the skin and deliver pain medications directly into the spinal fluid, providing targeted and continuous pain relief. Decompression Techniques: Laminectomy : This procedure involves removing a portion of the vertebral bone (lamina) to relieve pressure on the spinal cord or nerve roots, which can alleviate certain types of pain. Discectomy: This surgery involves removing a portion of a herniated or degenerated intervertebral disc to relieve pressure on the spinal nerve and reduce pain. 5- Surgical Correction of Structural Abnormalities: Joint Replacement : In cases of severe joint damage or arthritis, joint replacement surgery can be performed to alleviate pain and improve function. Spinal Fusion : This procedure involves Fusion two or more vertebrae in your  spine . . Insertion of a wound infiltration catheter Intrapleural injection

13. There are several other modalities for pain management besides traditional medication-based approaches. These include:  1-Physical Therapy and Exercise : Physical therapy and regular exercise can help manage pain by improving strength, flexibility, and range of motion. This can include techniques like stretching, strengthening exercises, and the use of heat/cold therapy. 2-Acupuncture : Acupuncture is a traditional Chinese medicine technique that involves the insertion of thin needles into specific points on the body to stimulate the natural pain-relieving mechanisms . 3-Massage Therapy : Massage can help reduce muscle tension, improve circulation, and promote relaxation , which can alleviate various types of pain.   4-Cognitive-Behavioral Therapy (CBT): CBT can help patients develop ** coping strategies and change negative thought patterns that can exacerbate pain perception . ** Come to terms with   5-Transcutaneous Electrical Nerve Stimulation ( TENS): TENS uses low-voltage electrical current to stimulate the nerves and potentially reduce pain signals. 6- Mindfulness and ** Meditation: Practices like mindfulness and meditation can help patients manage pain by reducing stress and promoting relaxation.   which  involves maintaining attention or awareness on the present moment without making judgments .  ** Continuous and profound contemplation or musing on a subject   7-Herbal and Dietary Supplements: Some natural supplements, like ** turmeric كركم , ** ginge r زنجبيل , or omega-3 fatty acids , may have anti-inflammatory properties that can help alleviate certain types of pain . ** plant of India having yellow flowers **Perennial plants having thick branching aromatic rhizomes and leafy reedlike stems Here are some links with more information on these alternative pain management modalities:  Physical Therapy for Pain Management: https://www.moveforwardpt.com/symptomsconditionsdetail.aspx?cid=a5d4328f-bf31-4302-b77f-0d2d99f1d0c6 1-Acupuncture for Pain Relief: https://www.nccih.nih.gov/health/acupuncture-in-depth 2-Massage Therapy for Pain Management: https://www.amtamassage.org/about/why-massage / 3-Cognitive-Behavioral Therapy for Chronic Pain: https://www.cci.health.wa.gov.au/Resources/Looking-for-Help/Chronic-Pain 4-TENS for Pain Relief : https://www.healthline.com/     ginge r زنجبيل turmeric كركم ,