Pain Management: Concepts, Evaluation, and Therapeutic Options
Lars Grimm, MD
July 21, 2014
Pain is a universally understood sign of disease; it is also the most common symptom that causes people to seek medical attention.[1] The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience [that is] associated with actual or potential tissue damage, or described in terms of such damage."[2] It is possible to describe different types of pain, and each pain type tends to have a different presentation. The history and physical examination help clinicians to identify these differences. Precise and systematic pain assessment is required to make the correct diagnosis and thus to establish the most efficacious treatment plan for patients who present with pain.[3]
Image courtesy of the Centers for Disease Control and Prevention (CDC).

The somatosensory system involves the conscious perception of touch, pressure, pain, temperature, position, movement, and vibration that arises from the muscles, joints, skin, and fascia.[4] This 3-neuron, 2-relay sites system carries sensations detected in the periphery through spinal cord-, brainstem-, and thalamic-relay nuclei pathways to the sensory cortex in the parietal lobe.[5] Impulses from receptors travel via sensory afferents to the dorsal root ganglia, the site of the first-order neuron cell bodies. [4,5] Their axons then travel ipsilaterally or contralaterally via the spinal cord. Second-order neuron cell bodies are located in the dorsal horn and medullary nuclei. Third-order neurons are located in the thalamus.[4,5] The functional magnetic resonance image (fMRI) shows blood oxygen level-dependent (BOLD) responses to pulsed peripheral ultrasonographic stimulation (PUNS-M) of somatosensory circuits in 5 patients (aMCC, anterior middle cingulate cortex; Cdt, caudate; In, insula; Op, parietal operculum; Put, putamen; S1, primary somatosensory cortex; SMA, supplementary motor area; SMg, supramarginal gyrus; Th, thalamus).
Image courtesy of Legon et al.[6]

Two major categories of pain are nociceptive and neuropathic (a third is psychogenic).[7,8] Nociception is a normal physiologic response to stimuli initiated by nociceptors, which detect mechanical, thermal, or chemical changes.[2,7,8] Nociceptive pain may be divided into three subtypes: superficial somatic pain from cutaneous nociceptors on the skin or superficial tissues; deep somatic pain from somatic nociceptors on ligaments, bones, blood vessels, and muscles; and visceral pain from visceral nociceptors within body organs. Somatic pain is typically localized and is described as throbbing, aching, or sharp/gnawing[7,8]; visceral pain is generally difficult to localize and is described as cramping,[8] achy, squeezing, or dragging.[7] The colonoscopy image demonstrates severe colitis that induced visceral nociceptive pain.

Neuropathic pain is pain induced by damage to the nerves themselves or by aberrant somatosensory pathways.[2,7,8] For example, herpes zoster (shown) can cause neuropathic pain via growth and inflammation within dermatomal nerves.[9] Hyperpathic symptoms of burning, tingling, or electrical sensations are classic for neuropathic pain; other sensations include itching, stinging, squeezing, and numbness.[7] Unfortunately, neuropathic pain is not traditionally responsive to standard pain medications; multimodal therapy may be beneficial and includes psychotherapy, physical therapy, pharmacotherapy with antidepressants/anticonvulsants, and surgery.[7,8]

Sensitization is an adaptive process in which innocuous stimuli produce an excessive response.[2] Repeated intense stimuli to damaged tissue lower the activation threshold and increase the frequency of firing of afferent nociceptors. Local inflammatory mediators contribute by recruiting additional nociceptors, which normally remain silent to routine stimuli.[7,8] For example, patients with sunburns (shown) often experience intense pain and discomfort with even very light touch because of sensitization of the pain fibers.[10] Central sensitization may also be partly responsible for the pathophysiology of chronic pain syndromes.[11,12]

Pain modulation can both enhance and dampen pain signals. Placebo can have a significant analgesic response, and anxiety can magnify the perceived stimuli. Descending signals from the frontal cortex and hypothalamus help modulate the ascending transmission of the pain signal by opiate receptors.[13,14] The image illustrates the pain pathways involved in pain transmission and modulation (CGRP, calcitonin gene-related peptide; EAA, excitatory amino acids; GABA, gamma-aminobutyric acid; Gal, galanin; 5-HT, serotonin; NA, noradrenaline; NPY, neuropeptide Y; SP, substance P).
Image courtesy of Tavares and Martins.[15]

Determining the best treatment course for pain management begins with identification of the intensity and duration of the pain.[3] Pain assessment relies largely upon the use of patient self-reports. Single-dimensional (rating pain intensity only) and multidimensional scales are available. Examples of single-dimensional scales include the IASP Faces Pain Rating Scale, Revised (top), and the Numeric Rating Scale (bottom). Multidimensional scales (eg, McGill Pain Questionnaire, Brief Pain Inventory) measure the pain intensity, the nature and location of the pain, and in some cases, the impact the pain is having on an activity or mood. The results obtained from these instruments must be viewed as guides, not absolutes.
Images courtesy of (top) IASP and (bottom) US Department of Veterans Affairs.

Although laboratory tests, imaging studies, and nerve or muscle conduction studies do not show pain in and of itself, these diagnostic modalities may help clinicians to identify the root cause of a patient's pain as well as provide important information for therapeutic planning. For example, this sagittal MRI of a patient with lumbosacral radiculopathy demonstrates herniations of the nucleus pulposus at L4-L5 and L5-S1 that are responsible for the patient's pain symptoms. Knowing the cause of patients' pain and being aware of the extent of an injury may help clinicians and patients to select specific procedural or other therapeutic interventions to manage the underlying condition and alleviate pain.
Image courtesy of Barton Branstetter, MD.

Medical management of pain proceeds in a stepwise fashion, as shown here (adapted from the World Health Organization "pain ladder").[18] Acute pain is typically treated with short courses of pharmacotherapy, whereas chronic pain may require long-acting medications or other interventional modalities.[19,20] For mild to moderate pain, nonnarcotic analgesics are used (eg, aspirin, acetaminophen, ibuprofen, naproxen, indomethacin, ketorolac); for moderate to severe pain, narcotic regimens are typically used (eg, codeine, oxycodone, morphine, hydromorphone, methadone, meperidine, fentanyl, tramadol).[20] Combination regimens that contain opioids and nonnarcotic analgesics provide additive pain control. Adjuvant medications include tricyclic antidepressants, antihistamines, and anticholinergics.

The pharmacology of pain control hinges on influencing one of several biochemical pathways. Many nonnarcotic analgesics inhibit cyclooxygenase, the enzyme that is responsible for the formation of prostaglandin, prostacyclin, and thromboxane. Opiate medications mimic endogenous opioid peptides. Opioids bind to one of three principal classes of opioid receptors (mu, kappa, delta) to produce centrally mediated analgesia. Tricyclic antidepressants are thought to potentiate the effect of opiates.[21]
Image courtesy of Lisa Wong, RPh.

Patient-controlled analgesia (PCA) allows patients to self-titrate their intravenous pain medication.[22] This method of pain control also allows more consistent administration of analgesia and shortens the interval between when the patient feels pain and when the analgesia is administered. PCA reduces the chances for medication errors, reduces nursing workload, increases patient autonomy, and provides objective data about the amount of medication a patient needs. It is traditionally used for postoperative patients and those with serious oncologic or hematologic diseases.
Image of a PCA infusion pump configured for epidural administration of fentanyl and bupivacaine for postoperative analgesia courtesy of Wikimedia Commons.

Transdermal patches provide controlled drug delivery with a lower potential for abuse than is present with oral analgesics,[23] a lower risk of adverse effects,[24] and a reduction in the frequency of dosing.[24] However, this form of drug delivery also includes the potential for skin reactions, a delayed onset of action, and a decrease in drug delivery from the loss of adhesive properties.[14] Transdermal patches are routinely used to treat conditions such as postherpetic neuralgia and chronic cancer pain.[25] The patches can be applied once every 12-24 hours.[23,25] Alternative forms of drug delivery used to treat patients with malignant pain include opiate-infused lollipops and buccal lozenges.[25]
Image courtesy of Lisa Wong, RPh.

Regional anesthesia with therapeutic injections can provide excellent relief for patients with localized pain and inflammation. Depending on the clinical scenario, nerve blocks may be used for therapeutic, sympathetic, diagnostic, prognostic, or prophylactic purposes.[26] For example, therapeutic injections permit a return to normal function by preventing the development of compensatory injuries. The exact procedural technique is dependent on the nerve involved, but the general principle involves the direct injection of a local anesthetic or corticosteroid into the perineural space. The image shows a patient undergoing a sural nerve block.

Depending on an operator's familiarity and the difficulty of accessing injection sites, image guidance may be used for direct visualization.[27] This computed tomography (CT)–guided image demonstrates an injection needle at L5 for a transforaminal nerve block, which can be performed for the diagnosis and treatment of radicular pain. CT, ultrasonographic, and fluoroscopic guidance allow more precise needle placement, thus decreasing the amount of injected drug and reducing the risk of complications. The technique is especially useful in patients with distorted native anatomy.
Image courtesy of Frank Gaillard, MBBS, MMed, FRANZCR, at Radiopaedia.org.

Surgical interventions are generally limited to patients with discrete deficits whose condition does not improve with conservative management.[28,29] Depending on the location of pain, patients will typically undergo a stepwise treatment course involving noninterventional management before being eligible for invasive therapy. Surgically implanted devices, such as intrathecal pumps (shown) and spinal cord stimulators, are available for use on a case-by-case basis.[28,29]
Image of an intrathecal baclofen pump and associated tubing (as well as separate tubing from a ventriculoperitoneal shunt) in a patient with hydrocephalus and new-onset nausea and pain courtesy of Yuranga Weerakkody, MBChB, FRANZCR, at Radiopaedia.org.

Spinal cord stimulation (SCS) (shown) is approved by the US Food and Drug Administration to relieve intractable pain.[30] Indications include failed back surgery syndrome, chronic painful peripheral neuropathy, complex regional pain syndromes, and intractable low back pain.[31,32] SCS may also be considered for postherpetic neuralgia.[33] The neurophysiologic mechanisms of SCS are not completely understood.[28,32] Experimental evidence supports a beneficial SCS effect at the dorsal horn level, whereby the hyperexcitability of wide-dynamic-range neurons is suppressed.[28,32] Evidence also exists for increased levels of GABA, serotonin, substance P, and acetylcholine.[32]
Image of a spinal cord stimulator implanted in the posterior epidural space of the thoracic spine courtesy of Wikimedia Commons.

A transcutaneous electrical nerve stimulation (TENS) unit (shown) is an adjuvant pain control device that provides pulsatile low-voltage electric impulses.[28,34-36] The proposed mechanisms by which TENS reduces pain are presynaptic signal inhibition, endogenous pain control, direct inhibition of abnormally excited nerves, and restoration of afferent inputs.[34,35] This method of pain control has been used for low back, arthritic, sympathetically mediated, neurogenic, visceral, and postoperative pain.[36] Although TENS is widely used and there is a great deal of anecdotal and observation-based evidence, there remains a paucity of randomized controlled trials confirming the effectiveness of this modality.[34,36]
Image courtesy of Wikimedia Commons.

Chronic, refractory pain is best managed with a multidisciplinary team approach that includes psychology, occupational therapy, physical therapy, osteopathic manipulative treatment, vocational rehabilitation, and relaxation training. Patients with chronic pain frequently seek complementary and alternative medicine treatment options as well, including acupuncture (shown), dietary supplements, and hypnosis.
Image courtesy of Wikimedia Commons.
